CN103619378B - wearable automatic injection device - Google Patents

Abstract

The exemplary embodiment of the present invention is provided for quick, controlled speed, with such as bolus by therapeutic agent injection Wearable automatic injection device in the patient.The exemplary embodiment of the present invention also provides assembling for the method for quick, controlled speed Wearable automatic injection device in the patient by therapeutic agent injection.The exemplary embodiment of the present invention is also provided therapeutic agent injection method in the patient using Wearable automatic injection device with quick, controlled speed.

Description

Wearable automatic injection device

Technical field

The application is that the non-of U.S. Provisional Patent Application Serial No. No.61/478,039 submitted on April 21st, 2011 faces When apply for and require the rights and interests of its priority.The U.S. Patent Application Serial Number that the application is also submitted to on April 21st, 2011 No.13/092,102（On January 26th, 2012 is disclosed as U.S. Patent bulletin No.2012-0022499A1）Related.Above-mentioned each The full content of application passes through to quote clearly to be herein incorporated.

Background technology

Automated injection device provide manually operable syringe replacement, for by therapeutic agent be injected in the patient and Allow patient oneself injection therapeutic agent.Automated injection device has been used in case of emergency injection of medicine, such as on injection kidney Parathyrine is to offset the impact of severe allergic reaction.Automated injection device is also described as anti-for injecting during having a heart attack Antiarrhythmic medicament and selectivity thrombolytics（See such as United States Patent (USP) No.3,910,260, No.4,004,577, No.4,689, 042nd, No.4,755,169 and No.4,795,433）.In such as United States Patent (USP) No.3,941,130, No.4,261,358, No.5, 085,642nd, No.5,092,843, No.5,102,393, No.5,267,963, No.6,149,626, No.6,270,479 and No.6, also illustrates various types of automated injection devices in 371,939 and PCT publication No.WO/2008/005315, above The full content of application is incorporated herein by reference.

Conventionally, automated injection device accommodate syringe, and operation when make syringe move forward and syringe needle from outer Shell projects, thus by the injection of therapeutic agent comprising in syringe in the patient.Conventional automated injection device includes hand-held Automated injection device and patch pump, it is automatic adhesion type and the automatic injector installed by patient.When using, comprise to treat The patch pump of agent is installed on the body of patient or clothes and is triggered to inject in the patient therapeutic agent.Patient is usual Fill the patch pump of routine before use.Additionally, some conventional patch pumps have the syringe needle of the exposure in pump, and it is thus desirable to Secondary aseptic packaging is to keep aseptic.

Content of the invention

The exemplary embodiment of the present invention is provided on the skin that can be attached to patient or clothes and with quick, controlled Speed, with such as bolus by therapeutic agent injection Wearable automatic injection device in the patient.The present invention's The method that exemplary embodiment also provides assembling Wearable automatic injection device.The exemplary embodiment of the present invention also provides and makes The method for quick, controllably injection therapeutic agent Wearable automatic injection device worn with patient.The present invention shows Example property Wearable automatic injection device reduces or eliminates usually to be felt using the patient of conventional automated injection device or perceives Burn feeling.The exemplary Wearable automatic injection device of the present invention keeps therapeutic agent aseptic（Such as syringe）, be easy to make With, can pre-filled, easily fabricated and/or not need disinfectant component.The Wearable that the exemplary embodiment of the present invention provides Automated injection device is used for injecting in the patient by any therapeutic agent, including but not limited to biologics, such as TNF α inhibitor, Antibody, insulin etc..

According to exemplary embodiment, a kind of Wearable automatic injection for injecting in the patient therapeutic agent is provided to fill Put.Described device includes shell, and this shell includes the patient contacting portions for contacting patient skin.Described device also includes noting Enter assembly, this fill assembly is movably disposed in shell and supports for the injection in the patient by therapeutic agent injection Interface.This fill assembly can project into outside shell in the not projecting punctured position to outside shell of grouting socket and grouting socket Move between extended position.Described device also includes：Container, it is arranged in shell, for preserving therapeutic agent；And piston Actuating mechanism, it is movably disposed in described container, for injecting to fill assembly therapeutic agent from container.Few Amass the therapeutic agent between 0.1 milliliter and 1.0 milliliters from container emitting body within the time of 30 seconds.

According to another exemplary embodiment, provide a kind of method therapeutic agent injected in the patient.Methods described includes There is provided Wearable automatic injection device, this device includes shell, and this shell includes the patient contact for contacting patient skin Part.Described device also includes fill assembly, and this fill assembly is movably disposed in shell and supports for controlling Treat agent injection grouting socket in the patient.This fill assembly can in the not projecting punctured position to outside shell of grouting socket and Move between the extended position that grouting socket projects into outside shell.Described device also includes：Container, it is arranged in shell, For preserving therapeutic agent；And piston actuated mechanism, it is movably disposed in described container, for therapeutic agent is calm Device injects in fill assembly.The patient contacting portions that methods described is included using shell are solid by Wearable automatic injection device Determine on the skin of patient.Methods described also includes volume existing in less than 30 seconds using Wearable automatic injection device Therapeutic agent between 0.1 milliliter and 1.0 milliliters injects in the patient.

According to another exemplary embodiment, provide a kind of method of assembling Wearable automatic injection device.Methods described Including the Part I assembling automated injection device in gnotobasiss, to preserve the sterile treatment agent of doses.Described side Method includes providing the one or more sterile barrier parts related to the Part I of device, with the assembling automated injection device phase Between and keep therapeutic agent fluid passage of being adopted during being injected in the patient aseptic afterwards.Methods described is additionally included in non- Assemble the Part II of automated injection device in gnotobasiss, keep the Part I of automated injection device aseptic simultaneously.

According to another exemplary embodiment, provide a kind of Wearable automatic injection device, therapeutic agent is injected to suffer from In person's body.Described device includes shell, and this shell includes the patient contacting portions for contacting patient skin.Described device is also wrapped Include assembly, this fill assembly is movably disposed in shell and supports for injecting in the patient therapeutic agent Grouting socket, this fill assembly can project into shell in the not projecting punctured position to outside shell of grouting socket and grouting socket Move between outer extended position.Described device also includes：Container, it is arranged in shell, for preserving therapeutic agent；And Piston actuated mechanism, it is movably disposed in described container, for injecting to fill assembly therapeutic agent from container. Described device also includes：Shrink trigger, its in response to Wearable automatic injection device from injection state to rear injection state State change and operate；And contracting mechanism, it is used for making fill assembly from injection by the described triggering shrinking trigger The extended position of state injects the punctured position of state after being automatically retracted to.From container emitting body within the time less than 30 seconds Amass the therapeutic agent between 0.1 milliliter and 1.0 milliliters.

According to another exemplary embodiment, provide a kind of method therapeutic agent injected in the patient.Methods described includes There is provided a kind of Wearable automatic injection device, this device includes shell, this shell includes the patient for contacting patient skin Contact portion.Described device also includes fill assembly, and this fill assembly is movably disposed in shell and supports to be used for By therapeutic agent injection grouting socket in the patient, this fill assembly can be in the not projecting punctured bit to outside shell of grouting socket Put and move and the extended position that grouting socket projects into outside shell between.Described device also includes：Container, it is arranged on shell In, for preserving therapeutic agent；And piston actuated mechanism, it is movably disposed in described container, for by therapeutic agent Inject to fill assembly from container.Described device also includes：Shrink trigger, it is in response to Wearable automatic injection device Operate from injection state to the state change of rear injection state；And contracting mechanism, it is used for by described contraction trigger Triggering make fill assembly from injection state extended position be automatically retracted to after inject state punctured position.Methods described bag Include and using the patient contacting portions of shell, Wearable automatic injection device is fixed on the skin of patient.Methods described is also wrapped Include using Wearable automatic injection device within the time less than 30 seconds by volume between 0.1 milliliter and 1.0 milliliters Therapeutic agent injects in the patient.

Brief description

By referring to combining the following description that accompanying drawing is made, the above and other purpose of exemplary embodiment, aspect, feature Will become apparent from advantage and can be better understood, in the accompanying drawings：

Figure 1A diagram includes being in the of the exemplary Wearable device of injection cartridge module of the pre-implant state of packaging End view and the first side view.

Figure 1B diagram is in the first end-view of the exemplary means of Figure 1A of pre-implant state before injection therapeutic agent With the first side view, wherein, in order to prepare to inject therapeutic agent, remove the lid covering grouting socket.

Fig. 1 C diagram be in the first end-view of the exemplary means of Figure 1A of injection state injecting therapeutic agent with First side view, wherein, grouting socket is contacted with patient body.

Fig. 1 D diagram be in the first end-view of the exemplary means of Figure 1A of injection state injecting therapeutic agent with First side view, wherein, the cylindrical portion of the device comprising doses therapeutic agent is launched forward in crust of the device.

Fig. 1 E diagram be in the first end-view of the exemplary means of Figure 1A of injection state injecting therapeutic agent with First side view, wherein, by piston actuater come the stopper of actuation means from the treatment of cylindrical portion discharging doses Agent.

Fig. 1 F diagram is in the first end-view of the exemplary means of Figure 1A of rear injection state after injection therapeutic agent With the first side view, wherein, grouting socket is contracted in the shell of device.

Fig. 2A diagram includes being in the of the exemplary Wearable device of the injector assembly of pre-implant state of packaging End view and the first side view.

Fig. 2 B diagram is in the first end-view of the exemplary means of Fig. 2A of pre-implant state before injection therapeutic agent With the first side view, wherein, in order to prepare to inject therapeutic agent, remove the lid covering grouting socket.

Fig. 2 C diagram be in the first end-view of the exemplary means of Fig. 2A of injection state injecting therapeutic agent with First side view, wherein, grouting socket is contacted with patient body.

Fig. 2 D diagram be in the first end-view of the exemplary means of Fig. 2A of injection state injecting therapeutic agent with First side view, wherein, the cylindrical portion of the device comprising doses therapeutic agent is launched forward in crust of the device.

Fig. 2 E diagram be in the first end-view of the exemplary means of Fig. 2A of injection state injecting therapeutic agent with First side view, wherein, by piston actuater come the stopper of actuation means from the treatment of cylindrical portion discharging doses Agent.

Fig. 2 F diagram is in the first end-view of the exemplary means of Fig. 2A of rear injection state after injection therapeutic agent With the first side view, wherein, grouting socket is contracted in the shell of device.

Fig. 3 is the flow chart of the illustrative methods assembling exemplary Wearable automatic injection device.

Fig. 4 is the flow chart of the illustrative methods using exemplary Wearable automatic injection device.

Fig. 5 is by therapeutic agent injection illustrative methods in the patient using exemplary Wearable automatic injection device Flow chart.

The exemplary of pre-implant state that be in that Fig. 6 A diagram is suitable to insert along straight line or be applied on patient body is worn Wear formula automated injection device.

Fig. 6 B is shown in the injection state being ready for injecting or is in by the injection of doses therapeutic agent in the patient During Fig. 6 A exemplary means.

Fig. 6 C be shown in completed by therapeutic agent injection in the patient after or therapeutic agent injection complete before from trouble The exemplary means of Fig. 6 A and 6B of rear injection state after device are removed with person.

Fig. 7 A diagram be in the pre-implant state being ready to be used by the patient be suitable to be rotatably inserted into exemplary wearable Formula automated injection device.

Fig. 7 B is shown in the injection state being ready for injecting or is in by the injection of doses therapeutic agent in the patient During Fig. 7 A exemplary means.

Fig. 7 C be shown in completed by therapeutic agent injection in the patient after or therapeutic agent injection complete before from trouble The exemplary means of Fig. 7 A and 7B of rear injection state after device are removed with person.

Fig. 8 is the flow chart of the illustrative methods assembling exemplary Wearable automatic injection device.

Fig. 9 is the flow chart of the illustrative methods using exemplary Wearable automatic injection device.

Figure 10 is by therapeutic agent injection illustrative methods in the patient using exemplary Wearable automatic injection device Flow chart.

The axonometric chart of Figure 11 A illustrative exemplary Wearable automatic injection device.

Figure 11 B illustrates exploded view, shows the part of the device of Figure 11 A.

The side view of Figure 12 A illustrative exemplary Wearable automatic injection device.

Figure 12 B illustrates axonometric chart, shows the part of the device of Figure 12 A.

The axonometric chart of Figure 13 A illustrative exemplary Wearable automatic injection device.

The top view of the device of Figure 13 B pictorial image 13A.

The side sectional view of the connecting gear of device of Figure 13 C pictorial image 13A.

Figure 14 A diagram includes the axonometric chart of the exemplary Wearable automatic injection device of exemplary ejection cartridge module.

The sectional side view of the exemplary ejection cartridge module of Figure 14 A that Figure 14 B diagram intercepts along longitudinal axis.

The top perspective view of the device of Figure 14 C pictorial image 14A.

Figure 15 illustrative exemplary cylindrical portion, wherein, the far-end of cylindrical portion supports the longitudinal axiss substantially along cylindrical portion The grouting socket that line extends.

Figure 16 illustrative exemplary cylindrical portion, wherein, the far-end of cylindrical portion supports the longitudinal axiss with respect to cylindrical portion Line is with the grouting socket of about 90 degree of extensions.

Figure 17 illustrative exemplary assembly, wherein, example adaptor will puncture through syringe needle and is connected to grouting socket.

Figure 18 illustrative exemplary assembly, wherein, fluid conduit systems will puncture through syringe needle and are connected to grouting socket.

Figure 19 illustrates for piercing through the exemplary connecting gear providing fluid conduit systems between syringe needle and grouting socket.

Figure 20 illustrates for piercing through the exemplary connecting gear providing fluid conduit systems between syringe needle and grouting socket.

Figure 21 illustrates for piercing through the exemplary connecting gear providing fluid conduit systems between syringe needle and grouting socket.

Figure 22 diagram may be used to the injector assembly or injection cartridge module shell in Wearable automatic injection device Interior Exemplary syringe or the injection tube actuator proceeding to extended position from punctured position.

Figure 23 diagram includes Part I, Part II and the hinge fraction that is arranged between the first and second parts Exemplary syringe or injection tube actuator.

Figure 24 is the axonometric chart of the exemplary automated injection device through lid, and this device is included using one or more fluids The piston actuated mechanism of conduit.

When Figure 25 diagram is injected by including the exemplary implantation system of flow restrictor in time（Second）Change Therapeutic agent cumulative volume（Milliliter）Chart.

Figure 26 is the exemplary automated injection device including the piston actuated mechanism using one or more fluid conduit systems Schematic diagram.

Figure 27 is the top view of the exemplary means of Figure 26.

The top view of Figure 28 illustrative exemplary automated injection device, shows and for the master cylinder of working fluid to be connected to Flow Limit The conduit of device processed, conduit flow restrictor being connected to stopper and the conduit via valve, master cylinder being connected to contracting mechanism.

Figure 29 illustrates the schematic diagram of the device of Figure 28.

Figure 30 is shown in the exemplary pressure in exemplary automated injection device after check-valves and after stopper（psi） In time（Second）The chart of change.

The side view of Figure 31 illustrative exemplary automated injection device, wherein, the shell bag of Wearable automatic injection device Include skin sensor foot.

Figure 32 A and 32B diagram makes grouting socket keep being in the punctured position of the inside the shell of exemplary automated injection device Exemplary grouting socket protection system.

Figure 33 A and 33B diagram makes grouting socket keep being in the punctured position of the inside the shell of exemplary automated injection device Another exemplary grouting socket protection system.

Figure 34 diagram makes grouting socket keep being in the another of the punctured position of inside the shell of exemplary automated injection device Exemplary grouting socket protection system.

Figure 35 A diagram makes grouting socket keep being in the another of the punctured position of inside the shell of exemplary automated injection device The axonometric chart of exemplary grouting socket protection system.

The top view of the exemplary grouting socket protection system of Figure 35 B pictorial image 35A.

First side view of the exemplary grouting socket protection system of Figure 35 C pictorial image 35A.

Second side view of the exemplary grouting socket protection system of Figure 35 D pictorial image 35A, wherein, automated injection device It is in injection state.

Second side view of the exemplary grouting socket protection system of Figure 35 E pictorial image 35A, wherein, automated injection device It is in pre-implant or rear injection state.

The first end that Figure 36 is shown in the exemplary Wearable device of the Figure 1A being in pre-implant state in outer package regards Figure and the first side view, wherein, the removing mechanism of protecting film is connected in a part for outer package.

The first end that Figure 37 is shown in the exemplary Wearable device of the Fig. 2A being in pre-implant state in outer package regards Figure and the first side view, wherein, the removing mechanism of protecting film is connected in a part for outer package.

Specific embodiment

Automated injection device provides the replacement to conventional manual operating syringe, for injecting therapeutic agent and allowing patient Oneself injection therapeutic agent.The exemplary embodiment of the present invention provides Wearable automatic injection device, and described device can be adhered to On the body or clothes of patient and with quickly controlled charge velocity（Such as one time bolus）Therapeutic agent is injected In the patient.The exemplary embodiment of the present invention also provides the method using Wearable automatic injection device, for quickly may be used Control ground injection therapeutic agent.

In the exemplary embodiment, about 0.1 milliliter can at about one second extremely to about 1 milliliter of volume or further amounts of therapeutic agent It is injected in the injection length section of about 12 hours.In the exemplary embodiment, for inject same volume scope injection when Between section can be in the range of about one second to about 30 seconds, but not limited to this exemplary range.In some exemplary embodiments, About 0.1 milliliter of therapeutic agent to about 1 milliliter of volume can be injected in the range of the time period from about 3 seconds to about 5 seconds.At some In exemplary embodiment, about 0.1 milliliter of therapeutic agent to about 1 milliliter of volume at about 20 seconds or can be shorter than quilt in time of 20 seconds Injection.

Exemplary Wearable automatic injection device be disposable, wieldy, can be pre-filled, and permissible Substantially or entirely eliminate the burn feeling usually experienced using the patient of Wearable automatic injection device.By exemplary automatic The quickly controlled charge velocity that injection device is realized can be by the pain related to a certain amount of therapeutic agent entering in patient tissue Pain is down to minimum.The exemplary time periods being rapidly injected realized by exemplary automated injection device can at about one second extremely In the range of about 30 seconds, but not limited to this exemplary range.Exemplary means can be injected in above time range The exemplary volume of therapeutic agent can be in the range of about 0.1 milliliter to about 1 milliliter, but not limited to this exemplary range.One In a little exemplary embodiments, about 0.1 milliliter of therapeutic agent to about 1 milliliter of volume can be in the time segment limit of about 3 seconds to about 5 seconds Inside it is injected into.In some exemplary embodiments, about 0.1 milliliter of therapeutic agent to about 1 milliliter of volume can be at about 20 seconds or short It is injected within the time period of 20 seconds.Additionally, exemplary means can advantageously provide linear injection curve, that is, with substantially constant Speed injection, and can will with regard to therapeutic agent injection length injection curve in flex point and suddenly change be minimized.

The exemplary embodiment of the present invention minimize the package dimension of exemplary automated injection device and provide can by than The scheme of example adjustment, described scheme has the configurable injection length that can be used for certain therapeutic agent range of viscosities and injection is bent Line.

The exemplary embodiment of the present invention not needing battery supply or can need electric current or charge to be operated In the case of other parts, therapeutic agent is injected in the patient.

The Wearable automatic injection device that the exemplary embodiment of the present invention provides is can be pre-filled and/or can be Pre-filled before patient is injected, described device keeps that therapeutic agent is aseptic, all therapeutic agent faces and patient contact Face（That is, one or more skin thorns of one or more of container, the device of therapeutic agent fluid conduit systems, grouting socket are comprised Enter surface, be arranged on one or more of fluid conduit systems partition etc.）Aseptic and therapeutic agent is adopted when being injected in the patient Injection channel is aseptic, in order to avoid needing disinfectant component, and solves to be carried out by by conventional hand-held automated injection device The sensorial patient that injection is led to is uncomfortable.Exemplary Wearable automatic injection device includes keeping aseptic and being therefore not required to Want the main treatment agent cylindrical portion of disinfectant component.

Exemplary automated injection device can be used for any suitable conveying injection depth injection therapeutic agent, for example subcutaneous Injection, intradermal injection, intramuscular injection, it is locally implanted.The Wearable automatic injection device that exemplary embodiment provides is permissible For injecting any therapeutic agent, including but not limited to, antibody, small molecule, insulin etc..The injection of exemplary automated injection device Device assembly can accommodate the TNF α inhibitor of doses.In the exemplary embodiment, TNF α inhibitor can be that human TNF alpha resists Body or its antigen-binding portion thereof.In the exemplary embodiment, human TNF alpha antibody or its antigen-binding portion thereof can be that A Damu is mono- Resist or goli mumab.

Referring to some illustrative embodiment, exemplary embodiment to be described.Although automatically noting described with reference to Wearable Injection device to describe exemplary embodiment come the liquid pharmaceutical to inject doses, but those of ordinary skill in the art should be bright In vain, exemplary embodiment is not limited to illustrative embodiment and exemplary automated injection device can be used for any suitable thing Matter is injected in the patient.Additionally, the part of exemplary automated injection device and manufacture and use exemplary automated injection device Method be not limited to illustrative embodiment described below.

I. the definition of exemplary term

Here part defines some terms to help understand exemplary embodiment.

The Wearable automatic injection device of exemplary embodiment can include the antibody of the present invention or " controlling of antibody moiety Treat effective dose " or " prevention effective dose "." therapeutically effective amount " refers to realize expectation under certain dosage and in the time period of needs Therapeutic outcome effective dose.The therapeutically effective amount of antibody, antibody moiety or other TNF α inhibitor can be according to such as disease shape State, age, sex and weight in patients and antibody, antibody moiety or other TNF α inhibitor can cause the Expected Response of patient The factors such as ability and change.The Beneficial Effect that therapeutically effective amount also refers to treat exceedes antibody, antibody moiety or other TNF α suppression The amount of any poisonous or adverse effect of agent." prevention effective dose " refers to realize the phase under certain dosage and in the time period of needs The effective dose of the prevention result hoped.Typically, since preventive dose before disease or commitment uses patient's internal, institute Will be less than therapeutically effective amount with prevention effective dose.

Term " material " and " therapeutic agent " refer to adopt exemplary automated injection device to inject with therapeutically effective amount Any kind of medicine in the patient, bioactivator, biological substance, chemical substance or biochemical substances.Exemplary materials bag Include but be not limited to liquid pharmaceutical.This medicament may include but be not limited to small molecule therapy agent.It is a kind of that therapeutic agent can be used for treatment Or multiple disease or health, for example, pain, cancer, Parkinson's disease etc..This kind of therapeutic agent can also include but is not limited to Ah Reach wooden monoclonal antibody（HUMIRA®）And protein fluid solution, such as fusion protein and enzyme.The example of protein solution include but It is not limited to α deoxyribonuclease（Dornase Alfa）, restructuring PDGF（Becaplermin）, Ai Keti fear this（Alteplase）、 α-L- iduronase（Mucopolysaccharide-L- iduronase）, gene tinea health（Ah method's Saite）, end intercalation Nai Sipo（A Fada Bei Boting）, becaplermin concentrate, beta color flourish（Interferon β-1b）, Clostridium botulinum toxin（A type bacillus botulinus）Angstrom Vertical spy（Rasburicase）, L-asparaginase（Asparaginase）, Epogen（Epoetin Alfa）, according to that Western general（TNF-α antagonist）, beta galactosidase A（Recombined human alpha-galactosidase A）, Infergen（Load interferon-alpha）, Gan Le Energy（Intederon Alpha-2a）, interleukin-1 receptor antagonist（Antril (Synergen)）, Clostridium botulinum（Type B botulinum toxin）, non-lattice The durative action preparation of department's booth（PEGylation filgrastim）, Niu Mijia（Oprelvekin）, rhG-CSF （Filgrastim）, denileukin diftitox（Interleukin fusion toxin）, Peg-IFN alpha-2b（Peg-IFN alpha-2b α -2a）, general Stay net（Aldesleukin）, α deoxyribonuclease（Dornase Alfa）, Rebif（Recombinant human interferon beta -1 α）, restructuring PDGF （Becaplermin）, reteplase（Zymoexcitator Deletion variants are dissolved in tissue-type fibrin）, Intederon Alpha-2a（Gene Recombinant alpha -2a interferon）, tenecteplase（Tissue plasminogen activator）And bolt essence injecta（Recombinant human activated protein C）, interleukin（IL1）Blocker（Lie Luoxipu）, grace general come（Luo meter Si booth）, U.S. letter sieve（3.2 methoxy poly (ethylene glycol)s promote red Erythropoietin-β）, C1- esterase inhibitor（C1 esterase inhibitor）, Chinese mugwort Du sulfur enzyme（Chinese mugwort Du's sulfuric ester）, alpha-glucosidase Recombined human（Alpha-glucosaccharase enzyme preparation）, Ao Ruixina（Orencia）, gala Glycosulfatase（Plus sulfur enzyme）, Kai Wangsi（Handkerchief Li Fuming）And gamma interferon 1-b（Chronic granulo matosiss curative gamma interferon 1-b）.

Protein in solution can also be immunoglobulin or their Fab, for example their antibody or Antigen-binding portion thereof.The example that can be used for the antibody of exemplary automated injection device includes but is not limited to chimeric antibody, inhuman anti- Body, human antibody, humanized antibody and single domain antibody（dAbs）.In the exemplary embodiment, immunoglobulin or theirs is anti- Former binding fragment is anti-TNF alpha and/or anti-IL-12 antibody（For example, it can be double variable domain immunoglobulin（DVD) IgTM）.Can be used for other examples of the method for exemplary embodiment and the immunoglobulin of composition or their Fab Son includes but is not limited to 1D4.7 (anti-IL-12/IL-23 antibody；Abbott)；2.5 (E) mg1 (anti-IL-18;Abbott Laboratories are public Department); 13C5.5（Anti- IL-13 antibody;Abbott);J695 (anti-IL-12;Abbott);Street rowdy not monoclonal antibody (Fab 2 Anti-TNF;Abbott);HUMIRA (adalimumab)；Abbott);Alemtuzumab (A Laizuo monoclonal antibody);ASIMO list Anti- (Fab);Erbitux (Cetuximab);Herceptin (Herceptin);Myoscint (spray Imciromab);Recurrent prostate cancer contrast agent (capromab pendetide);Remicade (English interest monoclonal antibody);(Ah former times is single for gift Lay Anti-);Mabthera (Rituximab);Simulect (basiliximab);AstraZeneca (palivizumab);Mercapto promise not (the non-list of promise Anti-);Sorel (Ao Mazuo monoclonal antibody);Zenapax (daclizumab);Ibritumomab (ibritumomab tiuxetan);Muromondb-CD3 (CD 3-resisting monoclonal antibody);Mouse anti-tumor monoclonal antibody (edrecolomab);Gemtuzumab ozogamicin (Ji trastuzumab difficult to understand);High Sharp monoclonal antibody (goli mumab);Plug trastuzumab (training plucked instrument trastuzumab);According to storehouse pearl monoclonal antibody (Yi Kuli monoclonal antibody); CNTO 1275 (excellent spy gram monoclonal antibody);Wei Ke replaces than (Victibix);Hectogram sand (tositumomab+131 iodine labeling tositumomab);And peace Wei Ting (Avastin).

The immunoglobulin of the method for exemplary embodiment and composition or the extra example of their Fab Son including but not limited to includes following one or more protein：D2E7 light chain variable region (SEQ ID NO:1), D2E7 weight Chain Variable Area (SEQ ID NO:2), D2E7 light chain variable region CDR3 (SEQ ID NO:3), D2E7 weight chain variable district Domain CDR3 (SEQ ID NO:4), D2E7 light chain variable region CDR2 (SEQ ID NO:5), D2E7 heavy chain variable domain CDR2 (SEQ ID NO:6), D2E7 light chain variable region CDR1 (SEQ ID NO:7), D2E7 heavy chain variable domain CDR1 (SEQ ID NO:8), 2SD4 light chain variable region (SEQ ID NO:9), 2SD4 heavy chain variable domain (SEQ ID NO: 10), 2SD4 light chain variable CDR3 (SEQ ID NO:11), EP B12 light chain variable CDR3 (SEQ ID NO: 12), VL10E4 light chain variable CDR3 (SEQ ID NO:13), VL100A9 light chain variable CDR3 (SEQ ID NO: 14), VLL100D2 light chain variable CDR3 (SEQ ID NO:15), VLL0F4 light chain variable CDR3 (SEQ ID NO: 16),LOE5 Light chain variable CDR3 (SEQ ID NO:17), VLLOG7 light chain variable CDR3 (SEQ ID NO:18), VLLOG9 light chain can Become CDR3 (SEQ ID NO:19), VLLOH1 light chain variable CDR3 (SEQ ID NO:20), VLLOH10 light chain variable CDR3 (SEQ ID NO:21), VL1B7 light chain variable CDR3 (SEQ ID NO:22), VL1C1 light chain variable CDR3 (SEQ ID NO:23), VL0.1F4 light chain variable CDR3 (SEQ ID NO:24), VL0.1H8 light chain variable CDR3 (SEQ ID NO:25), LOE7.A light chain variable CDR3 (SEQ ID NO:26), 2SD4 heavy chain variable domain CDR (SEQ ID NO: 27), VH1B11 heavy chain variable domain CDR (SEQ ID NO:28), VH1D8 heavy chain variable domain CDR (SEQ ID NO: 29), VH1A11 heavy chain variable domain CDR (SEQ ID NO:30), VH1B12 heavy chain variable domain CDR (SEQ ID NO: 31), VH1E4 heavy chain variable domain CDR (SEQ ID NO:32), VH1F6 heavy chain variable domain CDR (SEQ ID NO: 33), 3C-H2 heavy chain variable domain CDR (SEQ ID NO:, and VH1-D2.N heavy chain variable domain CDR (SEQ ID 34) NO: 35).

Term " human TNF alpha "（Here is abbreviated as hTNF α or is abbreviated as hTNF）Refer to as 17kD secreting type and 26kD Film combination type exist human cell factor, the biologically active form of described " human tumor necrosis factor-alpha " is by non-covalent bond 17kD The trimer of molecule is constituted.The structure of hTNF α is further described in the following documents：For example, Pennica, D. et al. (1984) Nature 312:724-729;Davis, J.M. et al. (1987) Biochem.26:1322-1326;And Jones, E.Y. et al. (1989) Nature 338:225-228.Term human tumor necrosis factor-alpha will include passing through standard The recombined human of recombinant expression method preparation or commercially available (R ＆ d system, Catalog Number No. 210-TA, Minneapolis, MN) swells Tumor necrosis factor-α (rhTNF α).TNF α is also referred to as TNF.

Term " TNF α inhibitor " refers to disturb the medicament of TNF α activity.This term also includes anti-TNF alpha human antibody（? This is interchangeably used TNF α antibody）With antibody moiety described here and United States Patent (USP) No.6,090,382,6,258, 562nd, each in those antibody described in 6,509,015,7,223,394 and 6,509,015.In one embodiment, The present invention use TNF α inhibitor be Anti-tnfa antibody or their fragment, including infliximab (Remicade, Johnson and Johnson;Described in United States Patent (USP) No. 5,656,272);CDP571 (Humanized monoclonal anti-TNF-α IgG4 antibody);CDP 870 (Humanized monoclonal anti-TNF-Alpha antibodies fragment);Anti-TNF dAb (Peptech company);CNTO 148 (goli mumabs;Centocor company, sees WO 02/12502 and U.S. 7,521,206 and U.S. 7,250, 165);And adalimumab (HUMIRA Abbott, people's anti-TNF mAb are described in US 6,090,382 D2E7).Describing in United States Patent (USP) No. 6,593,458,6,498,237,6,451,983 and 6,448,380 can be at this Extra TNF antibody used in bright.In another embodiment, TNF α inhibitor is TNF fusion protein, and such as benefit plug is general (Enbrel, Amgen;Described in WO 91/03553 and WO 09/406476).In another embodiment, TNF α suppression Preparation is restructuring TNF conjugated protein (r-TBP-I) (Xue Lannuo company).

In one embodiment, term " TNF α inhibitor " does not include infliximab.In one embodiment, term " TNF α inhibitor " does not include adalimumab.In another embodiment, term " TNF α inhibitor " does not include A Da wood list Resist and infliximab.

In one embodiment, term " TNF α inhibitor " do not include benefit plug general, selectively do not include adalimumab, Infliximab and adalimumab and infliximab.

In one embodiment, term " TNF α antibody " does not include infliximab.In one embodiment, term " TNF α antibody " does not include adalimumab.In another embodiment, term " TNF α antibody " do not include adalimumab and Infliximab.

" antibody " refers to the immunoglobulin molecules being generally made up of four polypeptide chains, and it passes through disulfide bond by two weights （H）Chain and two are light（L）Chain is connected with each other.Each heavy chain is by weight chain variable district（It is abbreviated as HCVR or VH herein）And light chain constant District's groups become.CH is made up of tri- domains of CH1, CH2 and CH3.Each light chain is by light chain variable district（It is abbreviated as herein LCVR or VL）With constant region of light chain composition.Constant region of light chain is made up of a CL domain.VH and VL domain can be further It is subdivided into referred to as complementary determining region（CDR）Hypervariable region, be wherein studded with more conservative region, referred to as framework region（FR）.Each VH and VL forms arrangement from amino terminal to C-terminal in the following order by three CDR and four FR：FR1、CDR1、FR2、 CDR2、FR3、CDR3、FR4.In United States Patent (USP) No.6,090,382, No.6,258,562 and No.6,509,015 in more detail Describe the antibody of the present invention.

" antigen-binding portion thereof " of term antibody（Or referred to as " antibody moiety "）Refer to keep to antigen（Such as hTNF α）One or more fragments of the antibody of ability of specific binding.The fragment of full length antibody can carry out the antigen binding of antibody Function.The example of the binding fragment being included in " antigen-binding portion thereof " of term antibody includes（i）Fab fragment, by VL, VH, The monovalent fragment of CL and CH1 domain composition；（ii）F (ab') 2 fragment, comprises by the two of disulfide bond in hinge region The bivalent fragment of Fab fragment；（iii）The Fd fragment being made up of VH and CH1 domain；（iv）VL and VH structure by single armed antibody The Fv fragment of domain composition；（v）DAb fragment（Ward et al.（1989）Nature 341:544-546）, it is by VH or VL domain Composition；（vi）Individually complementary determining region（CDR）；And（vii）Double variable regions immunoglobulin（DVD-Ig）.In addition although Fv fragment（VL and VH）Two domains pass through single gene code, but they can make them by recombination method Wherein VL and VH area can be become match to form monovalent molecule（Referred to as scFv（scFv）；See, for example, Bird et al. （1988）Science 242:423-426;And Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883）Single protein chain synthesis connector connect.Such single-chain antibody is also included within the " antigen of term antibody In bound fraction ".Also include the other forms of single-chain antibody, such as bispecific antibody.Bispecific antibody is bivalence, bispecific Antibody, wherein, single polypeptide chain expresses VH and VL domain, but can not be made in same chain using being short so that very much The connector of two domain pairings, by the complementary domain pairing in this reinforcement structure domain and other chains, and produces two antigens Connection site（See, for example, Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448； Poljak et al. (1994) Structure 2:1121-1123）.In United States Patent (USP) No.6,090,382, No.6,258,562 and It is more fully described the antibody moiety of the present invention in No.6,509,015.

Term " recombinant human antibody " is referred to be prepared by recombination method, expresses, produces or detached human antibody, for example Antibody using the recombinant expression carrier expression of transfection to host cell（It is described further below）, detached anti-from recombinant Body, combination human antibody storehouse（It is described further below）, from by transgenic for human immunoglobulin gene animal（Such as mice） Detached antibody（See, for example, Taylor et al. (1992) Nucl. Acids Res. 20:6287）Or by including exempting from people Epidemic disease globulin gene sequence montage is prepared, expresses, is produced or detached antibody to any other method of other DNA sequence.This The recombinant human antibody of sample has variable region and constant region from human germline immunoglobulin's sequence.However, in some embodiments In, make mutation outside such people's recombinant antibodies generating body（Or when the animal using transgenic behaviour Ig sequence, there is internal body Cell mutation）, and may be naturally occurring in whole in vivo by the aminoacid sequence in the VH and VL area of this recombinant antibodies In human antibody germline, although it is derived from and related to people's germline VH and VL sequence.

Such chimeric antibody, humanized antibody, human antibody and double can be prepared by recombinant DNA technology known in the art Specific antibody, such as using PCT international application No. PCT/US86/02269；European patent application No. 184,187；Europe Patent application No. 171,496；European patent application No. 173,494；PCT international publication No. WO 86/01533；The U.S. Patent No. 4,816,567；European patent application No. 125,023；Better et al. (1988) Science 240:1041- 1043;Liu et al.. (1987) Proc. Natl. Acad. Sci. USA 84:3439-3443；Liu et al. (1987) J. Immunol. 139:3521-3526；Sun et al. (1987) Proc. Natl. Acad. Sci. USA 84:214- 218；Nishimura et al. (1987) Cancer Res. 47:999-1005；Wood et al. (1985) Nature 314: 446-449；Shaw et al. (1988) J. Natl. Cancer Inst. 80:1553-1559；Morrison (1985) Science 229:1202-1207；Oi et al. (1986) BioTechniques 4:214；United States Patent (USP) No. 5,225,539； Jones et al. (1986) Nature 321:552-525；Verhoeyan et al. (1988) Science 239:1534；And Beidler et al. (1988) J. Immunol. 141:4053-4060, Queen et al. (1989) Proc. Natl. Acad. Sci. USA 86:10029-10033 (1989)；United States Patent (USP) No. 5,530,101；United States Patent (USP) No. 5,585,089； U.S. 5,693,761；U.S. 5,693,762；WO 90/07861;And the method described in U.S. 5,225,539.

Term " dosage " " or " consumption " refer to preferably use the Wearable automatic injection device injection patient of the present invention Internal material（Such as TNF α inhibitor）Amount.In one embodiment, dosage includes TNF α inhibitor or adalimumab Effective dose, for example include but is not limited to, 20mg, 30mg, 40mg, 50mg, 60mg, 70mg, 80mg, 90mg, 100mg, 110mg, 120mg, 130mg, 140mg, 150mg and 160mg.

Term " administration " refers to injected material（Such as Anti-tnfa antibody）To realize therapeutic purposes（For example, treat rheumatism Property arthritis）.

Term " administration rule " description material（Such as TNF α inhibitor）Treatment process, such as in long period and/or Run through the treatment process of therapeutic process, for example, first week injection the first dosage TNF α inhibitor and subsequently with every two weeks one The TNF α inhibitor of secondary administration rule injection the second dosage.

Term " therapy " refers to treat the therapy and such as TNF α disease harmful to it, such as rheumatic arthritis The prevention of the therapy of disease or suppressing method.

Term " patient " or " user " refer to inject any of therapeutic agent using exemplary automated injection device The animal of species, people or inhuman.

What term " Wearable automatic injection device " and " Wearable automatic injector " referred to that patient wears makes Patient can be by being fastened directly to be fastened on medicated clothing on his or her skin or by Wearable device Wearable device On make this device and patient body couple to come oneself injection treatment effective dose therapeutic agent device, wherein, Wearable Device is, including a mechanism, when engaging this mechanism, therapeutic agent to be automatically injected patient's body with the difference of conventional syringe Interior.

Term " syringe " and " injection tube " include quilt before distributing or be sold to patient or other Non-medical specialty personnel Fill with the aseptic cylindrical portion of doses therapeutic agent, for injecting in the patient therapeutic agent.Form note in cylindrical portion In the exemplary embodiment of emitter, the far-end of cylindrical portion can be connected to aseptic syringe needle or multiple aseptic syringe needle.In cylindrical part Divide in the another exemplary embodiment forming injection tube, the far-end of cylindrical portion can be not coupled to aseptic syringe needle or multiple nothing Acicula head.In some exemplary embodiments, syringe can be injection tube, and pre-attached formula syringe needle or multiple syringe needle are connected to it Cylindrical portion.

The exemplary cylindrical portion of syringe or injection tube can be formed by any suitable material, including but not limited to poly- Compound material（For example, medical grade polymer）, metal, glass, silicon crystal etc..In the exemplary embodiment, cylindrical portion can Be rigid or can be in for preserving one or more flexible bag of therapeutic agent in the form of.

Here can also be realized using injection cartridge module with reference to the exemplary embodiment that injector assembly describes.Similar Ground, here can also be realized using injector assembly with reference to the exemplary embodiment of injection cartridge module description.

Term " container " refers to be used for keeping certain used in exemplary Wearable automatic injection device The syringe of dosage treatment agent or injection tube.

Term " biasing mechanism " refers to directly or indirectly provide the one of power to piston and/or stopper in automated injection device Individual or multiple parts.In the exemplary embodiment, biasing mechanism can include one or more springs（For example, coil spring, Compression spring）.Biasing mechanism may be at contraction state before injection therapeutic agent, and is released in injection period with cylinder Shape partly middle activated forwards stopper.In a further exemplary embodiment, biasing mechanism can include chemical gas generator, example As, expanded foam, it was in the unexpanded stage before injection therapeutic agent, and expanded in injection period with cylindrical portion Activated forwards stopper.In other exemplary embodiments of the invention, biasing mechanism can adopt hydraulic pressure, the compressed gas of working fluid Gas pressure, osmotic pressure, hydrogel expand etc..

Term " injection " refers to therapeutic agent is transported to or injects any mechanism in the patient.The exemplary machine of injection System or technology include but is not limited to subcutaneous injection, corium injection, intramuscular injection, local injection etc..

Term " injection position " refers on patient body or interior position, at this position or near exemplary automatic note Injection device is coupled with patient to inject therapeutic agent.

Term " grouting socket " refer to be inserted in Wearable automatic injection device in the patient, be applied to patient's body Couple on body or with patient body with one or more parts in the patient by the injection of doses therapeutic agent.In exemplary reality Apply in example, grouting socket can be directly coupled to or contact the injector assembly preserving doses therapeutic agent or injection tube group Part.In a further exemplary embodiment, grouting socket can be coupled indirectly to injector assembly or injection cartridge module, for example via Pierce through syringe needle.In the exemplary embodiment, connecting gear can be in fluid communication piercing through to provide between syringe needle and grouting socket.Show Example property grouting socket can include but is not limited to single syringe needle, multiple syringe needle, the syringe needle being connected on pipe, be connected on pipe Multiple syringe needles, multiple micropin（Including dissolvable micropin）, needleless gauze piece, needleless paster etc..

Term " micropin " and " microneedle " refer to small-sized injection needle, and it has to be applied to therapeutic agent is injected patient Any size of internal required technology.The length of exemplary micropin in the range of about 1 micron to about 5mm, but can be not limited to This exemplary range.

Term " puncture syringe needle " refers to be connected to or contact injector assembly or note in Wearable automatic injection device One or more sharp component of shooting cylinder assembly（For example, one or more syringe needles and/or one or more sharp shaped material）, it is used for The therapeutic agent of doses is transported to grouting socket from injector assembly or injection cartridge module, grouting socket is then by therapeutic agent Injection is in the patient.In the exemplary embodiment, pierce through syringe needle to be not inserted into or act on patient.In another exemplary embodiment In, pierce through syringe needle and may be inserted into or act on patient body.

In the exemplary Wearable automatic injection device including injector assembly, piercing through syringe needle can be directly coupled to The cylindrical portion of syringe and being in fluid communication with cylindrical portion.In the exemplary Wearable including injection cartridge module certainly In dynamic injection device, piercing through syringe needle can be disposed separately with the cylindrical portion of injection tube, and for example, piercing through syringe needle can be set In grouting socket button or connecting gear.During injection stage, puncture syringe needle may be inserted into the cylindrical portion of injection tube In far-end, to pierce through foundation fluid communication between syringe needle and cylindrical portion.

Before term " pre-implant state " refers to start to inject the therapeutic agent accommodating in a device, Wearable is noted automatically The state of injection device.

Term " injection state " refers to inject Wearable automatic injection device during the therapeutic agent accommodating in a device One or more states.

Term " afterwards inject state " refer to complete to inject accommodate the therapeutic agent for the treatment of effective dose in a device and Removed device from patient before completing to inject the therapeutic agent for the treatment of effective dose.

Term " quick " refers to the charge velocity of a certain amount of therapeutic agent.In the exemplary embodiment, about 0.1 milliliter to about 1 milliliter of volume or further amounts of therapeutic agent can be injected in the injection length section of about a second to about 12 hours.In example In property embodiment, for inject same volume scope injection length section can in the range of about one second to about 30 seconds, but Not limited to this exemplary range.In some exemplary embodiments, about 0.1 milliliter of therapeutic agent to about 1 milliliter of volume can be It is injected in the range of the time period of about 3 seconds to about 5 seconds.In some exemplary embodiments, about 0.1 milliliter to about 1 milliliter volume Therapeutic agent can be injected in about 20 seconds or the time being shorter than 20 seconds.

In some exemplary embodiments, two or more automated injection devices can simultaneously coupled or use, with The therapeutic agent that in the range of the time period of about one second to about 30 seconds, injected slurry volume is more than 1 milliliter.

In some exemplary embodiments, two or more injection tubes can be arranged in automated injection device, with It is injected simultaneously into the therapeutic agent that volume is more than 1 milliliter in the range of the time period of about one second to about 30 seconds.

In some exemplary embodiments, two or more syringes can be arranged in automated injection device, with It is injected simultaneously into the therapeutic agent that volume is more than 1 milliliter in the range of the time period of about one second to about 30 seconds.

Term " clothes " refers to cover on patient skin and exemplary Wearable automatic injection device can couple Or it is attached to any suitable covering thereon.Thus, in the middle of this part clothes can be formed between device and patient skin Layer and can be used for for device being directly coupled to patient skin.In the exemplary embodiment, this part clothes can be patient's skin Underclothes on skin, for example, nylon sock.In a further exemplary embodiment, this part clothes can be covering on patient skin Cover material, including but not limited to, medical science adhesive plaster, binder etc..In a further exemplary embodiment, this part clothes can be that device is attached The coupling mechanism near patient skin, including but not limited to, sleeve in a part for patient body, skin can be enclosed within Band, band（Such as binding tape with hook-and-loop fasteners）Deng.

As used herein, term " near-end " refer to when hold exemplary automated injection device make its against patient so that When injection or simulation injection, the farthest part of the injection position on patient body of described device, end or part.

As used herein, term " far-end " refer to when hold exemplary automated injection device make its against patient so that When injection or simulation injection, the nearest part of the injection position on patient body of described device, end or part.

As used herein, term " equal to " broadly represent and be exactly equal to or be approximately equal in certain tolerance.

II. exemplary automated injection device

Reference picture 1-14 describes some exemplary Wearable automatic injection device.The description of reference picture 15-21 can be used for showing Example property Wearable automatic injection device is with some exemplary needle system of delivering therapeutic agents.The description of reference picture 22-31 is available Activated with some example piston discharging therapeutic agent from syringe or injection tube in exemplary Wearable automatic injection device System and grouting socket pinch system.The description of reference picture 32-35 can be used for exemplary Wearable automatic injection device to keep Grouting socket rear injection state after injection it is in some exemplary grouting socket protection systems of punctured position.

Exemplary Wearable automatic injection device can be using injection cartridge module（As shown in Figure 1A -1F）Or syringe group Part（As shown in figs. 2 a-2f）, doses therapeutic agent in the patient can be injected by grouting socket for preserving.In figure Some in figures in 1A-1F and Fig. 2A -2F, grouting socket is depicted as single injection needle.However, exemplary grouting socket is not It is limited to the illustrative embodiment shown in Figure 1A -1F and Fig. 2A -2F.

Figure 1A -1F diagram includes can be used for injection the wearing of cartridge module in the patient by the injection of doses therapeutic agent Wear the exemplary embodiment of formula automated injection device 100.Figure 1A diagram is in the exemplary wearable of the pre-implant state of packaging First end-view of formula device 100 and the first side view.Figure 1B diagram is in the first of the exemplary means 100 of pre-implant state End-view and the first side view, wherein, in order to prepare to inject this agent therapeutic agent to patient, remove the lid covering grouting socket. Fig. 1 C diagram is in the first end-view of exemplary means 100 and first side view of the injection state injecting therapeutic agent, Wherein, grouting socket is projected from the shell of device to be coupled with patient body.Fig. 1 D diagram is in the note injecting therapeutic agent Enter the first end-view and first side view of the exemplary means 100 of state, wherein, comprise the cylindrical part of doses therapeutic agent Divide and launch forward in the shell of device 100.Fig. 1 E diagram is in the exemplary means of the injection state injecting therapeutic agent 100 the first end-view and the first side view, wherein, by piston actuater come actuated plug from cylindrical portion discharge this one Determine the therapeutic agent of dosage.Fig. 1 F diagram is in the first end of the exemplary means 100 of rear injection state after injection therapeutic agent View and the first side view, wherein, grouting socket is contracted in the shell of device 100.

Wearable automatic injection device 100 can include shell 102, and shell 102 includes multiple walls to limit wherein For accommodating interior section or the chamber of injection cartridge module.In the exemplary embodiment, one or more breach or opening are permissible It is arranged on the side-walls of shell 102 and may be configured to receive injection cartridge module.In the exemplary embodiment, in assembling During automatic injection assembling, injection cartridge module can be slipped in the chamber of shell 102 by this breach or opening.In exemplary reality Apply in example, cover part can be configured so that for covering breach or opening.

In the exemplary embodiment, shell 102 can have elongated construction, but those of ordinary skill in the art should Understand that shell 102 can have for housing any of the cylindrical portion accommodating doses therapeutic agent in the patient to be implanted Suitably sized, shape and configuration.In the exemplary embodiment, shell 102 can be configured so that and is connected to formation patient contact Independent lid on partial base.In the exemplary embodiment, shell 102 can be formed by any suitable material, including But it is not limited to plastics and other known material.

The shell 102 of Wearable automatic injection device 100 can be included along the patient contacting portion at the bottom of shell 102 Divide the adhesive layer 124 disposing, the bottom of shell 102 is placed as the medicated clothing of neighbouring patient skin or patient.Exemplary at some In embodiment, adhesive layer 124 can be configured on the body of patient, thus shell 102 is attached to patient to inject The therapeutic agent of doses.Adhesive layer 124 can include non-sticky removing mechanism 126, for example, do not have sticking auricle.Patient can To catch and to pull non-sticky removing mechanism 126, to remove Wearable automatic injection device on the skin of patient or clothes 100.

Before using Wearable automatic injection device 100, for instance in the packed state shown in Figure 1A, adhesive layer 124 can be covered by protecting film 128, and it keeps the bond property of adhesive layer 124.Protecting film 128 can include removing mechanism 130, patient can catch and pull removing mechanism 130 to remove protecting film 128 from adhesive layer 124.So expose adhesive layer 124 so that shell 102 can be attached to by patient by being placed on that side with adhesive layer 124 on skin or medicated clothing On his or her skin or this part clothes.

Shell 102 can be housed in near-end（Farthest apart from grouting socket）And far-end（Nearest apart from grouting socket）Between big The injection of therapeutic agent cartridge module that body extends along longitudinal axes L.Injection cartridge module can include for preserve to be implanted in the patient The therapeutic agent of doses 108 cylindrical portion 106.Cylindrical portion 106 can be in near-end（Farthest apart from grouting socket）With Far-end（Nearest apart from grouting socket）Between substantially extend along a longitudinal axis.In the exemplary embodiment, cylindrical portion 106 is permissible It is the general cylindrical component with circular cross section, but those of ordinary skill in the art should be understood that cylindrical portion 106 can To have any suitable shape or configuration.

In the exemplary embodiment, cylindrical portion 106 can be fixed in shell 102, so that injection process will not Make cylindrical portion 106 mobile with respect to shell 102 in shell 102.In a further exemplary embodiment, cylindrical portion 106 is Just（That is, the pre-implant state before injection therapeutic agent）May be at the punctured position of the proximal retraction towards device 100（As Shown in Figure 1A -1C）, and the injection state during injection therapeutic agent can be actuated to the remote extension towards device 100 Extended position.Can the proximal end of cylindrical portion 106 or near arrange stopper 110, this agent therapeutic agent is sealed in cylinder To discharge this agent therapeutic agent from cylindrical portion 106 in shape part 106 and to this agent therapeutic agent applying power.Stopper 110 can be in cylinder Move towards the far-end of cylindrical portion 106 in shape part 106, so that the injection state during injection therapeutic agent is from cylindrical portion 106 this agent therapeutic agent of discharge.In the exemplary embodiment, stopper 110 can be configured to play sealing therapeutic agent and from cylinder simultaneously The effect of therapeutic agent is pushed out in shape part 106.In a further exemplary embodiment, stopper can be configured so that therapeutic agent is close It is enclosed in cylindrical portion 106, and single plunger can be set or piston rod comes to stopper applying power, so that from cylindrical portion Therapeutic agent is pushed out in 106.

Injection cartridge module its proximal end or near can include piston actuater 112, its be used in cylindrical portion 106 Optionally towards far-end activated forwards stopper 110, to will be received in the treatment of the treatment effective dose in cylindrical portion 106 Agent is injected in the patient.Piston actuater 112 can carry out actuated plug 110 using energy stores and controlled energy relieving mechanism. In the exemplary embodiment, piston actuater 112 may be located at cylindrical portion 106 outside or is positioned partially or entirely in cylindrical part Divide in 106.In the exemplary embodiment, piston actuater 112 can be by using positioned at stopper 110 and piston actuater 112 Between piston directly or indirectly drive stopper 110.

In the exemplary embodiment, piston actuater 112 can include biasing mechanism, such as spring, and it is before injection Shrink and be released in injection period, with activated forwards stopper 110 in cylindrical portion 106.In another exemplary embodiment In, piston actuater 112 can include chemical gas generator, for example, expanded foam, it is in unexpanded rank before injection Section, and expand in injection period with activated forwards stopper 110 in cylindrical portion 106.In other exemplary embodiments of the invention, live Plug actuator 112 can be expanded using the hydraulic pressure of working fluid, the gas pressure of compressed gas, osmotic pressure, hydrogel Deng.

In the exemplary embodiment, piston actuater 112 can in cylindrical portion 106 in a substantially linear fashion（I.e. Substantially invariable speed）Move forward.This allows therapeutic agent to be injected into substantially invariable charge velocity.Piston actuater 112 Can include or can be connected to and can be used for energy absorption（For example, initial release energy）Damping mechanism, and in piston Actuator 112 provides more controlled energy release during releasing energy.Controlled energy release can produce substantially linear Injection curve, i.e. substantially invariable therapeutic agent charge velocity in time, and injection rate suddenly change can be prevented.

In the exemplary embodiment, piston actuater 112 can be returned using the one or more fluids comprising working fluid Road, wherein, the hydraulic pressure of working fluid is to stopper applying power with moving plug in the cylindrical portion of injection tube.Damping mechanism Can be using the flow restrictor between workflow body source and stopper in fluid circuit.

In a further exemplary embodiment, piston actuater 112 can adopt biasing mechanism, for example, helical spring or spiral shell Rotation shape compression spring.Damping mechanism can adopt viscous damper, Swiss lever eacapement, inversioless gain Deng.

In a further exemplary embodiment, piston actuater 112 can be using the stepping electricity being connected to gear train assembly Motivation, to provide constant linear injection curve.

Injection cartridge module can include injection tube retainer 114 in its far-end or attachment, and injection tube retainer 114 is permissible Lid 115 including partition with for partition.Partition can be to can pierce material layer, and it is arranged to neighbouring cylindrical portion 106 Far-end so that sealing cylindrical portion 106 in therapeutic agent.When intact, partition can seal in cylindrical portion 106 Therapeutic agent.When being pierced through by sharp component（For example pierce through syringe needle）When, partition can allow therapeutic agent to leave cylindrical portion 106 to go forward side by side Enter to pierce through syringe needle.Partition can be formed by the material that can be pierced needle pierces.Lid can be configured so that and protectively covers Lid partition, in case the pierced syringe needle of partition surprisingly pierces through when device 100 is in the pre-implant state of packaging as shown in Figure 1A. In the exemplary embodiment, injection tube retainer 114 can also include lid, is arranged on injection tube stop protectively to cover Puncture syringe needle near part 114, thus prevents the partition quilt when device 100 is in the pre-implant state of packaging as shown in Figure 1A Pierce through syringe needle surprisingly to pierce through.

The shell 102 of Wearable automatic injection device 100 can also house supporting and be configured to pierce through patient skin The grouting socket button 116 of grouting socket 118.In the exemplary embodiment, grouting socket 118 can be with the longitudinal direction of device 100 The alignment of axis L-orthogonal ground.In the exemplary embodiment, grouting socket 118 can by being arranged in grouting socket button 116 or Grouting socket support detached with grouting socket button 116（Not shown）It is held in place.

In some exemplary embodiments, grouting socket 118 can include having and be adapted to pierce through patient skin and controlled with injecting Treat any suitably sized, shape of agent and one or more injection needles of configuration.In the exemplary embodiment, grouting socket 118 can include single injection needle（Illustrated by the solid line in Figure 1A -1F）.In a further exemplary embodiment, grouting socket 118 can include two or more injection needles（By the shown in phantom extra syringe needle in Figure 1A -1F）.In some other examples In property embodiment, grouting socket 118 can include the needleless liner being locally implanted for executing therapeutic agent（needle-free pad）And/or needleless paster（needle-free patch）.

The suitable injection needle that can be used for exemplary grouting socket can have and is configured to or is chosen as offer and be suitable to The length of the injection depth of required treatment.Subcutaneous injection generally pierces about six to ten millimeters of skin.In the exemplary embodiment, show Example property injection needle can have the length of about 12mm and can inject skin to the depth of about 7mm.Real in other examples Apply in example, exemplary ejection syringe needle can have the length being suitable to corium, muscle treatment etc..Suitable injection needle can have Be adapted to provide for enough mechanical strengths wall thickness, be adapted to allow for required material flow patient is felt to be down to simultaneously minimum Diameter and be suitable to required treatment and feel to be down to minimum tip geometry by patient simultaneously.

In the case of pharmaceutically acceptable, exemplary ejection syringe needle can be coated as needed, patient is felt to be down to Low.Grouting socket 118 can be covered with exempts from mechanically damaged and passes through grouting socket lid 122（For example, rigid needle shield, Flexible needle housing or both）Keep being in aseptic or under the conditions of being uninfected by.Grouting socket lid 122 can also make by grouting socket 118 The fluid conduit systems forming or being connected to grouting socket 118 keep aseptic.

Grouting socket button 116 can also support puncture syringe needle 120, pierce through syringe needle 120 be configured to pierce through partition and Set up with cylindrical portion 106 and be in fluid communication.In the exemplary embodiment, piercing through syringe needle 120 can be with the longitudinal axis of device 100 L abreast aligns.Pierce through syringe needle 120 and can have any suitably sized, shape being adapted to pierce through partition and configuration, and not It is limited to illustrative embodiment.

In the exemplary embodiment, grouting socket 118 and puncture syringe needle 120 can be via the masters of grouting socket button 116 Body is mutually connected and is in fluid communication.In a further exemplary embodiment, grouting socket 118 and puncture syringe needle 120 can be via one Individual or multiple fluid conduit systems（Do not draw）Mutually it is connected and be in fluid communication.In a further exemplary embodiment, grouting socket 118 He Pierce through syringe needle 120 directly can mutually be connected and be in fluid communication.

In the exemplary embodiment, the pre-implant state before injection therapeutic agent, grouting socket button 116 is with respect to outer Shell 102 may be at vertically convex position so that grouting socket button 116 is from the top boss of shell 102, such as Figure 1A and Shown in 1B.In this position, grouting socket 118 can be contracted in shell 102 and can not act on patient body.In this position Put, pierce through syringe needle 120 and can be vertically aligned above the partition in injection tube retainer 114 and partition can not be pierced through. When injection process starts, can for example pass through the user of device or automatically press down on grouting socket button 116.This Grouting socket button 116 can be shifted onto vertical recessed location with respect to shell 102, closer to patient body, so that note Incoming interface button 116 no longer from the top boss of shell 102, as shown in Fig. 1 C-1E.In this position, grouting socket 118 can be from Base projections of shell 102 and can be inserted into or act on patient body.In this position, piercing through syringe needle 120 can be with note Partition in shooting cylinder retainer 114 aligns and can pierce through partition.

In the exemplary embodiment, initial partition can be separated with grouting socket button 116.In this embodiment, when Supporting partition injection tube retainer 114 in shell 102 towards grouting socket button 116 advances when, puncture syringe needle 120 permissible Pierce through partition.That is, the pre-implant state before injection therapeutic agent, pierce through syringe needle 120 and can open with separates, thus There is not fluid communication in cylindrical portion 106 and the grouting socket 118 being connected to grouting socket button 116 between.In injection shape State, cylindrical portion 106 can be towards the distal advancement of device 100 in shell 102, so that pierce through syringe needle 120 can pierce Wear partition and set up fluid communication in cylindrical portion 106 and the grouting socket 118 being connected to grouting socket button 116 between. When applying pressure in the injection state during therapeutic agent of injecting to the therapeutic agent of doses, this fluid communication can allow one The therapeutic agent determining dosage flows to patient from cylindrical portion 116 by piercing through syringe needle 120 and grouting socket 118.

Referring now to Fig. 1 F, in the exemplary embodiment, the shell 102 of Wearable automatic injection device 100 can wrap Include skin sensor foot 132, its be on the close patient body be housed in shell 102 or interior injection phase partly lower or interior Structure.Injection therapeutic agent before and during, skin sensor foot 132 be maintained in a part for the downside of shell 102 or Form this part.When Wearable automatic injection device 100 is attached on patient body or interior injection phase and being opened When dynamic, skin sensor foot 132 can move freely, but is constrained by injection phase.When removing Wearable from injection phase During automated injection device 100, no matter whether therapeutic agent injects completes, and skin sensor foot 132 is no longer constrained, and extend and Project into outside the edge of shell 102.This starts contraction trigger then.When contraction trigger is activated, contracting mechanism is received Contracting grouting socket 120, grouting socket button 116 can also be increased to vertically convex position from vertical lower position by this, thus Make grouting socket button 116 from the top boss of shell 102 and grouting socket 118 is contracted in shell 102.

Figure 1A diagram is in pre-implant state（For example packaged）Wearable automatic injection device 100, wherein, tubular Part 106 can be by pre-filled and/or can the pre-filled therapeutic agent with doses 108 and be in punctured bit to be used Put.Doses are comprised in the inner space that cylindrical portion 106 can limit between the wall of cylindrical portion 106 and stopper 110 108 therapeutic agent.In an embodiment, can store when released can be with the energy of actuated plug 110 for piston actuater 112. Grouting socket button 116 can be positioned partially in shell 102 at the vertically convex position above injection phase, and injects Interface 118 can be contracted in shell 102.The projection from shell 102 top for the grouting socket button 116 can provide for patient can The visual instruction that Worn type automated injection device 100 is operated.

Figure 1B diagram is in the Wearable automatic injection device 100 of pre-implant state, wherein, removes grouting socket lid 122 and partition.In the exemplary embodiment, protecting film 128 can include being connected to grouting socket lid 122 and injection tube stop Partition in part 114 and the coupling member piercing through needle cover.Coupling member can include tether, auricle or other link mechanism. When protecting film 128 is removed, the coupling member of protecting film 128 can remove grouting socket lid 122 and injection tube retainer Partition in 114 and puncture needle cover.

Fig. 1 C diagram is in the Wearable automatic injection device 100 of the injection state during injection therapeutic agent, wherein, note Incoming interface button 116 is in the vertical lower position in shell 102.In vertical lower position, grouting socket button 116 can position Depression above injection phase in the shell 102 or vertical lower position, and grouting socket 118 can be by shell 102 One or more breach or opening from shell 102 projection so that grouting socket 118 can be in trouble in injection phase Person's body couples.In the exemplary embodiment it is provided that cover is covering breach or opening.In exemplary embodiment In, the breach of shell or opening can be relative with the patient contacting portions of shell, so that grouting socket button 116 is permissible It is vertically lowered to inject therapeutic agent.In the state that is vertically lowered, grouting socket button 116 can not from the top boss of shell 102, This visual instruction that can operate to patient's offer Wearable automatic injection device 100.In another exemplary embodiment In, breach in shell 102 or opening can not be arranged to relative with patient contacting portions and may be located at outer on the contrary In the side wall of shell.In some exemplary embodiments can laterally or the low mobile grouting socket button 116 of level is injecting treatment Agent.

Fig. 1 D diagram is in the Wearable automatic injection device 100 of the injection state during injection therapeutic agent, wherein, bag The cylindrical portion 106 of the therapeutic agent containing doses 108 is deployed into forward extending position from punctured position in the shell of device 100 Put.The advance of cylindrical portion 106 is so that the far-end of cylindrical portion 106 or injection tube retainer 114 come close to or in contact with injection Interface button 116.In the exemplary embodiment, pierce through syringe needle 120 can pierce through be maintained in injection tube retainer 114 every Piece, set up between cylindrical portion 106 and grouting socket 118 to be in fluid communication.

Fig. 1 E diagram is in the Wearable automatic injection device 100 of the injection state during injection therapeutic agent, wherein, lives Plug actuator 112 is triggered with moving plug 110.The triggering of piston actuater 112 can be to store in release plunger actuator 112 Energy so that towards the far-end moving plug 110 of device 100 in cylindrical portion 106.The movement of stopper 110 can be passed through The far-end of cylindrical portion 106 projects the therapeutic agent of doses from cylindrical portion 106.Any suitable mechanism may be used to Triggering piston actuater 112, this mechanism includes but is not limited to, and is connected to grouting socket button 116 and is connect by pressing injection Mouthful button 116 or by removing the coupling member that grouting socket lid 122 starts, the trigger button that can be started by patient etc..

Fig. 1 F diagram injects state after being in（For example, control after the therapeutic agent of injection treatment effective dose or in injection Before the therapeutic agent for the treatment of effective dose after patient removes Wearable automatic injection device 100）Wearable automatic injection Device 100, wherein, grouting socket button 116 is in vertically convex position.In vertically convex position, grouting socket button 116 can With elevated position above injection phase or vertically it is positioned partially in shell 102 at convex position, and grouting socket 118 can be contracted in shell 102.The a part of of grouting socket button 116 can be from the top boss of shell 102, with to trouble Person provides Wearable automatic injection device assembly 100 to be operated（State is injected after being in）Visual instruction.Tubular Part 106 can be not filled by therapeutic agent and injection actuator 112 can no longer storage energy.When removing device from injection phase When 100, skin sensor foot 132 can extend from the bottom of shell 102.

Shell 102 can include for grouting socket button 116 injecting state from vertical bottom（Shown in Fig. 1 C-1E）From Move and be increased to vertically convex rear injection state（Illustrate in figure 1f）Contracting mechanism.In the exemplary embodiment, shrinker Structure can include biasing mechanism, such as spring, and it biases injection cartridge module and makes it away from injecting position when contracting mechanism is triggered Put.

Upon being activated, shrink trigger and can trigger contracting mechanism, so that by grouting socket button 116 from vertical bottom State is increased to vertically convex state.In the exemplary embodiment, stopper 110 and/or piston actuater 112 can include connecting To the coupling member shrinking trigger.Coupling member can include tether, auricle or other link mechanism.Coupling member can have There is suitable length, thus when stopper 110 is moved into the end of cylindrical portion 106（To inject controlling of doses Treat agent）, link mechanism's trigger latch, then start and shrink trigger.In a further exemplary embodiment, skin sensor foot The extension of 132 bottoms from shell 102 can start contraction trigger.

In the exemplary embodiment, contracting mechanism can include triggering upon being activated the administration of contracting mechanism and terminate to shrink Trigger.When the therapeutic agent of the treatment effective dose in Wearable automatic injection device 100 is injected into, administration can be started Terminate to shrink trigger.In the exemplary embodiment, administration end contraction trigger can include breech lock, for example, elastoplast Hook, it is released when therapeutic agent injection completes.Contracting mechanism can also include removing contraction trigger in advance, and it is being activated When trigger contracting mechanism.Automatic when removing Wearable from injection phase before being fully injected into the therapeutic agent for the treatment of effective dose During injection device 100, removing contraction trigger in advance can be activated.In the exemplary embodiment, remove contraction triggering in advance Device can include breech lock, for example, elastoplast hook, its quilt when removing Wearable automatic injection device 100 from injection phase Release.Contracting mechanism comes from injection phase in response to administration end contraction trigger and in response to removing contraction trigger in advance Automatically shrink injection cartridge module.

In the exemplary embodiment, grouting socket button 116 is increased to vertically convex position can lead to pierce through syringe needle 120 are bent upwards, and thus prevent from undesirably reusing puncture syringe needle and Wearable automatic injection device.

Fig. 2A -2F diagram includes can be used for wearing doses therapeutic agent injection injector assembly in the patient Wear the exemplary embodiment of formula automated injection device 200.Fig. 2A diagram is in the exemplary wearable of the pre-implant state of packaging First end-view of formula device 200 and the first side view.Fig. 2 B diagram is in the first of the exemplary means 200 of pre-implant state End-view and the first side view, wherein, in order to prepare to inject therapeutic agent, remove the lid covering grouting socket.At Fig. 2 C diagram In the first end-view and the first side view that inject the exemplary means 200 of the injection state of therapeutic agent, wherein, injection connects Mouth is projected from the shell of device to be coupled with patient body.Fig. 2 D diagram is in the example of the injection state injecting therapeutic agent First end-view of property device 200 and the first side view, wherein, the cylindrical portion comprising doses therapeutic agent is in device 200 Shell in launch forward.Fig. 2 E diagram is in the first end of the exemplary means 200 of the injection state injecting therapeutic agent View and the first side view, wherein, discharge the controlling of this doses come actuated plug from cylindrical portion by piston actuater Treat agent.Fig. 2 F diagram is in first end-view and first of the exemplary means 200 of rear injection state after injection therapeutic agent Side view, wherein, grouting socket is contracted in the shell of device 200.

Wearable automatic injection device 200 can include the shell 202 for accommodating exemplary ejection device assembly.Can wear Wear formula automated injection device 200 and can include shell 202, shell 202 includes multiple walls to limit wherein for accommodating injection The interior section of device assembly or chamber.In the exemplary embodiment, one or more breach or opening can be arranged on shell 202 side-walls and may be configured to receive exemplary ejection device assembly.In the exemplary embodiment, automatically note in assembling During penetrating assembling, injector assembly can be slipped in the chamber of shell 202 by this breach or opening.In exemplary embodiment In, cover part can be configured so that for covering breach or opening.

In the exemplary embodiment, shell 202 can have elongated construction, but those of ordinary skill in the art should Understand that shell 202 can have for housing any of the cylindrical portion accommodating doses therapeutic agent in the patient to be implanted Suitably sized, shape and configuration.In the exemplary embodiment, shell 202 can be configured so that and is connected to formation patient contact Independent lid on partial base.In the exemplary embodiment, shell 202 can be formed by any suitable material, including But it is not limited to plastics and other known material.

The shell 202 of Wearable automatic injection device 200 can be included along the patient contacting portion at the bottom of shell 202 Divide the adhesive layer 224 disposing, the bottom of shell 202 is placed as the medicated clothing of neighbouring patient skin or patient.Exemplary at some In embodiment, adhesive layer 224 can be configured on the skin of patient, thus shell 202 is attached to patient to inject The therapeutic agent of doses.Adhesive layer 224 can include non-sticky removing mechanism 226, for example, do not have sticking auricle.Patient can To catch and to pull non-sticky removing mechanism 226, to remove Wearable automatic injection device on the skin of patient or clothes 200.

Before using Wearable automatic injection device 200, for instance in the packed state shown in Fig. 2A, adhesive layer 224 can be covered by protecting film 228, and it keeps the bond property of adhesive layer 224.Protecting film 228 can include removing mechanism 230 （Such as auricle）, patient can catch and pull removing mechanism 230 to remove protecting film 228 from adhesive layer 224.So expose viscous Close layer 224 so that patient can be by that side with adhesive layer 224 is placed on skin or medicated clothing will be attached for shell 202 It is connected on his or her skin or this part clothes.

Shell 202 can be housed in near-end（Farthest apart from grouting socket）And far-end（Nearest apart from grouting socket）Between big The injector assembly that body extends along longitudinal axes L.Injector assembly can be included for preserving in the patient certain to be implanted The cylindrical portion 206 of the therapeutic agent of dosage 208.Cylindrical portion 206 can be in near-end（Farthest apart from grouting socket）And far-end（Away from Nearest from grouting socket）Between substantially extend along a longitudinal axis.In the exemplary embodiment, cylindrical portion 206 can be had The general cylindrical component of circular cross section, but those of ordinary skill in the art should be understood that cylindrical portion 206 can have Any suitable shape or configuration.

In the exemplary embodiment, cylindrical portion 206 can be fixed in shell 202, so that injection process will not Make cylindrical portion 206 mobile with respect to shell 202 in shell 202.In a further exemplary embodiment, cylindrical portion 206 is Just（That is, the pre-implant state before injection therapeutic agent）May be at the punctured position of the proximal retraction towards device 200（As Shown in Fig. 2A -2C）, and the injection state during injection therapeutic agent can be actuated to the remote extension towards device 200 Extended position.

Can the proximal end of cylindrical portion 206 or near arrange stopper 210, this agent therapeutic agent is sealed in cylindrical part Divide in 206 and to this agent therapeutic agent applying power to discharge this agent therapeutic agent from cylindrical portion 206.Stopper 210 can be in cylindrical part Divide in 206 and move towards the far-end of cylindrical portion 206, so that the injection state during injection therapeutic agent is from cylindrical portion 206 Discharge this agent therapeutic agent.In the exemplary embodiment, stopper 210 can be configured to play sealing therapeutic agent and from cylindrical part simultaneously Divide the effect pushing out therapeutic agent in 206.In a further exemplary embodiment, stopper can be configured so that and is sealed in therapeutic agent In cylindrical portion 206, and single plunger can be set or piston rod comes to stopper applying power, so that from cylindrical portion 206 In push out therapeutic agent.

Injector assembly its far-end or near can include the distal portions 214 of syringe retainer or syringe, The distal portions 214 of syringe retainer or syringe can include piercing through syringe needle 220.By piercing through needle cover 234（For example soft Property needle housing, rigid needle shield or both）, pierce through syringe needle 220 and can be covered with and exempt from mechanically damaged and keep being in aseptic bar Under part, that is, under conditions for sterilization.Puncture needle skull 234 can also keep being formed by puncture syringe needle 220 or be connected to puncture syringe needle 220 Fluid passage aseptic.In the exemplary embodiment, piercing needle 220 can be abreast right with the longitudinal axes L of device 200 Together.Piercing needle 220 can have any suitably sized, shape being adapted to pierce through partition and configuration, and is not limited to explanation Property embodiment.

Injector assembly its proximal end or near can include piston actuater 212, its be used in cylindrical portion 206 Optionally towards far-end activated forwards stopper 210, to will be received in the treatment of the treatment effective dose in cylindrical portion 206 Agent is injected in the patient.Piston actuater 212 can carry out actuated plug 210 using energy stores and controlled energy relieving mechanism. In the exemplary embodiment, piston actuater 212 may be located at cylindrical portion 206 outside or is positioned partially or entirely in cylindrical part Divide in 206.In the exemplary embodiment, piston actuater 212 can be by using positioned at stopper 210 and piston actuater 212 Between piston directly or indirectly drive stopper 210.

In the exemplary embodiment, piston actuater 212 can include biasing mechanism, such as spring, and it is in injection treatment Shrink before agent and be released in injection period, with activated forwards stopper 210 in cylindrical portion 206.In another exemplary In embodiment, piston actuater 212 can include chemical gas generator, for example, expanded foam, it is before injection therapeutic agent It is in the unexpanded stage, and expand with activated forwards stopper 210 in cylindrical portion 206 in injection period.In other examples Property embodiment in, piston actuater 212 can adopt the hydraulic pressure of working fluid, the gas pressure of compressed gas, osmotic pressure Power, hydrogel expansion etc..

In the exemplary embodiment, piston actuater 212 can in cylindrical portion 206 in a substantially linear fashion（I.e. Substantially invariable speed）Move forward.This can allow therapeutic agent to be injected into substantially invariable charge velocity.Piston actuater 212 can include or can be connected to can be used for energy absorption（For example, initial release energy）Damping mechanism, and living Plug actuator 212 provides more controlled energy release during releasing energy.Controlled energy release can produce substantially linear Injection curve, i.e. substantially invariable therapeutic agent charge velocity in time, and injection rate suddenly change can be prevented.? In exemplary embodiment, piston actuater 212 can adopt the hydraulic pressure of working fluid, and damping mechanism can adopt position The flow restrictor between working fluid and stopper 210 in fluid passage.In a further exemplary embodiment, piston actuater 212 can adopt biasing mechanism, and damping mechanism can adopt viscous damper, Swiss lever eacapement, no return force Square escapement etc..In a further exemplary embodiment, piston actuater 212 can be using the step being connected to gear train assembly Enter motor, to provide constant linear injection curve.

The shell 202 of Wearable automatic injection device 200 can also house supporting and is configured to inject on skin to be controlled The grouting socket button treated agent or inject the grouting socket 218 of any desired depth in skin or by skin by therapeutic agent 216.In the exemplary embodiment, grouting socket 218 orthogonally can be alignd with the longitudinal axes L of device 200.In exemplary reality Apply in example, grouting socket 218 can be by being arranged in grouting socket button 216 or note detached with grouting socket button 216 Incoming interface support（Not shown）It is held in place.

In some exemplary embodiments, grouting socket 218 can include having and is adapted to pierce through patient skin to note Enter any suitably sized, shape of therapeutic agent and one or more injection needles of configuration, and be not limited to illustrative enforcement Example.In the exemplary embodiment, grouting socket 218 can include single injection needle（Illustrated by the solid line in Fig. 2A -2F）.? In another exemplary embodiment, grouting socket 218 can include two or more injection needles（Shown by the dotted line in Fig. 2A -2F Go out extra syringe needle）.In some other examples embodiments, grouting socket 218 can include the office for executing therapeutic agent The needleless liner of portion's injection and/or needleless paster.

The suitable injection needle that can be used for exemplary grouting socket can have and is configured to or is chosen as offer and be suitable to The length of the injection depth of required treatment.Subcutaneous injection generally pierces about six to ten millimeters of skin.In the exemplary embodiment, show Example property injection needle can have the length of about 12mm and can inject skin to the depth of about 7mm.Real in other examples Apply in example, exemplary ejection syringe needle can have the length being suitable to corium, muscle treatment etc..Suitable injection needle can have Be adapted to provide for enough mechanical strengths wall thickness, be adapted to allow for required material flow patient is felt to be down to simultaneously minimum Diameter and be suitable to required treatment and feel to be down to minimum tip geometry by patient simultaneously.

In the case of pharmaceutically acceptable, exemplary ejection syringe needle can be coated as needed, patient is felt to be down to Low.Grouting socket 218 can be covered with exempts from mechanically damaged and passes through grouting socket lid 222（For example, rigid needle shield, Flexible needle housing or both）Keep being under aseptic condition, that is, under conditions for sterilization.Grouting socket lid 222 can also make to be connect by injection The fluid conduit systems that mouth 218 is formed or coupled to grouting socket 218 keep aseptic.

Grouting socket button 216 can also be included positioned at the pierceable partition piercing through near syringe needle 220.In pre-implant shape State, pierces through syringe needle 220 and does not pierce through partition, thus prevents cylindrical portion 206 and pierces through fluid communication between syringe needle 220.In injection State, when by sharp component（For example pierce through syringe needle 220）During puncture, partition can allow therapeutic agent to leave cylindrical portion 206 simultaneously Enter and pierce through syringe needle 220.In the exemplary embodiment, partition can be enclosed in sterile barrier for one or more lids 215. When piercing through syringe needle 220 puncture partition, lid 215 can be pierced.

In the exemplary embodiment, grouting socket 218 and puncture syringe needle 220 can be via the masters of grouting socket button 216 Body is mutually connected and is in fluid communication.In a further exemplary embodiment, grouting socket 218 and puncture syringe needle 220 can be via one Individual or multiple fluid conduit systems（Do not draw）Mutually it is connected and be in fluid communication.In a further exemplary embodiment, grouting socket 218 He Pierce through syringe needle 220 directly can mutually be connected and be in fluid communication.

In the exemplary embodiment, pre-implant state before injection, grouting socket button 216 is with respect to shell 202 May be at vertically convex position, so that grouting socket button 216 is from the top boss of shell 202, as Fig. 2A and 2B institute Show.In this position, grouting socket 218 can be contracted in shell 202 and can not couple with patient body.In this position, Pierce through syringe needle 220 to be vertically aligned below the partition in syringe retainer 214 and partition can not be pierced through.In note When entering process and starting, can for example pass through the user of device or automatically press down on grouting socket button 216.This is permissible Grouting socket button 216 is shifted onto vertical recessed location with respect to shell 202, closer to patient body, so that injection connects Mouthful button 216 no longer from the top boss of shell 202, as shown in figures 2 c-2e.In this position, grouting socket 218 can be from shell 202 base projections and can for example by pierce patient body and couple with patient body.In this position, pierce through syringe needle 220 can be alignd with the partition in syringe retainer 214 and can pierce through partition.

In the exemplary embodiment, initial partition can be separated with grouting socket button 216.In this embodiment, when Keep pierce through syringe needle 220 syringe retainer 214 in shell 202 towards partition advances when, puncture syringe needle 220 can pierce through Partition.That is, pre-implant state before injection, pierce through syringe needle 220 and can open with separates, thus in cylindrical portion There is not fluid communication between 206 and the grouting socket 218 being connected to grouting socket button 216.In injection state, cylindrical portion 206 can towards the distal advancement of device 200 in shell 202 so that pierce through syringe needle 220 can pierce through partition and Set up between cylindrical portion 206 and the grouting socket 218 being connected to grouting socket button 216 and be in fluid communication.When in injection treatment Injection state during agent to the therapeutic agent of doses apply pressure when, this is in fluid communication and can allow the treatment of doses Agent passes through to pierce through syringe needle 220 from cylindrical portion 206 and grouting socket 218 flows to patient.

Referring now to Fig. 2 F, in the exemplary embodiment, the shell 202 of Wearable automatic injection device 200 can wrap Include skin sensor foot 232, it is the partly lower or interior structure of the close injection phase being housed in shell 202.Control in injection Before treating agent and injection period, skin sensor foot 232 is maintained in a part for the downside of shell 202 or forms this part. When Wearable automatic injection device 200 is attached to injection phase and is activated, skin sensor foot 232 can be free Mobile, but constrained by injection phase.When removing Wearable automatic injection device 200 from injection phase, no matter therapeutic agent Whether injection completes, and skin sensor foot 232 is no longer constrained, and extends and project into outside the edge of shell 202.This continues And start contraction trigger.When contraction trigger is activated, contracting mechanism shrinks grouting socket 220, and this can also will inject Interface button 216 is increased to vertically convex position from vertical lower position, so that grouting socket button 216 is from shell 202 Top boss and grouting socket 218 be contracted in shell 202.

Fig. 2A diagram is in pre-implant state（For example packaged）Wearable automatic injection device 200, wherein, tubular Part 206 by the pre-filled therapeutic agent with doses 208 and can be in punctured position to be used.Cylindrical portion 206 The therapeutic agent comprising doses 208 in the inner space that can limit between the wall of cylindrical portion 206 and stopper 210.? In embodiment, piston actuater 212 can store when released can be with the energy of actuated plug 210.Grouting socket button 216 Can be positioned partially in shell 202 at vertically convex position above injection phase, and grouting socket 218 can shrink In shell 202.The projection from shell 202 top for the grouting socket button 216 can provide Wearable automatic injection for patient The visual instruction that device 200 is operated.

Fig. 2 B diagram is in the Wearable automatic injection device 200 of the pre-implant state before injection therapeutic agent, wherein, Remove grouting socket lid 222 and partition lid.In the exemplary embodiment, protecting film 228 can include being connected to grouting socket lid 222nd, the coupling member of the puncture needle cover in partition lid and syringe retainer 214.Coupling member can include tether, auricle Or other links mechanism.When protecting film 228 is removed, the coupling member of protecting film 228 can remove grouting socket lid automatically 222nd, the puncture needle cover in partition lid and syringe retainer 214.

Fig. 2 C diagram is in the Wearable automatic injection device 200 of the injection state during injection therapeutic agent, wherein, note Incoming interface button 216 is in the vertical lower position in shell 202.In vertical lower position, grouting socket button 216 can position Depression above injection phase in the shell 202 or vertical lower position, and grouting socket 218 can be by shell 202 One or more breach or opening from shell 202 projection so that grouting socket 218 can be in trouble in injection phase Person's body couples.In the exemplary embodiment it is provided that cover is covering breach or opening.In exemplary embodiment In, the breach of shell or opening can be relative with the patient contacting portions of shell, so that grouting socket button 216 is permissible It is vertically lowered to inject therapeutic agent.In the state that is vertically lowered, grouting socket button 216 can not from the top boss of shell 202, This visual instruction that can operate to patient's offer Wearable automatic injection device 200.In another exemplary embodiment In, breach in shell 202 or opening can not be arranged to relative with patient contacting portions and may be located at outer on the contrary In the side wall of shell.In some exemplary embodiments can laterally or the low mobile grouting socket button 216 of level is injecting treatment Agent.

Fig. 2 D diagram is in the Wearable automatic injection device 200 of the injection state during injection therapeutic agent, wherein, bag The cylindrical portion 206 of the therapeutic agent containing doses 208 is deployed into forward extending position from punctured position in the shell of device 200 Put.The advance of cylindrical portion 206 is so that the far-end of cylindrical portion 206 or syringe retainer 214 come close to or in contact with injection Interface button 216.In the exemplary embodiment, pierce through syringe needle 220 can pierce through be maintained in syringe retainer 214 every Piece, set up between cylindrical portion 206 and grouting socket 218 to be in fluid communication.

Fig. 2 E diagram is in the Wearable automatic injection device 200 of the injection state during injection therapeutic agent, wherein, lives Plug actuator 212 is triggered with moving plug 210.The triggering of piston actuater 212 can be to store in release plunger actuator 212 Energy so that towards the far-end moving plug 210 of device 200 in cylindrical portion 206.The movement of stopper 210 can be passed through The far-end of cylindrical portion 206 projects the therapeutic agent of doses from cylindrical portion 206.Any suitable mechanism may be used to Triggering piston actuater 212, this mechanism includes but is not limited to, and is connected to grouting socket button 216 and is connect by pressing injection Mouthful button 216 or by removing the coupling member that grouting socket lid 222 starts, the trigger button that can be started by patient etc..

Fig. 2 F diagram is in the rear injection state after injection therapeutic agent（For example, in the treatment of injection treatment effective dose After agent or injection treatment effective dose therapeutic agent before after patient removes Wearable automatic injection device 200）'s Wearable automatic injection device 200, wherein, grouting socket button 216 is in vertically convex position.In vertically convex position, Grouting socket button 216 can elevated position above injection phase or be vertically positioned partially at shell at convex position In 202, and grouting socket 218 can be contracted in shell 202.The a part of of grouting socket button 216 can be from shell 202 Top boss, with to patient provide Wearable automatic injection device assembly 200 operated（Shape is injected after being in State）Visual instruction.Cylindrical portion 206 can be not filled by therapeutic agent and injection actuator 212 can no longer storage energy.When When injection phase removes device 200, skin sensor foot 232 can extend from the bottom of shell 202.

Shell 202 can include for grouting socket button 216 injecting state from vertical bottom（Shown in Fig. 2 C-2E）From Move and be increased to vertically convex rear injection state（Illustrate in fig. 2f）Contracting mechanism.In the exemplary embodiment, shrinker Structure can include biasing mechanism, such as spring, and it biases injector assembly and makes it away from injecting position when contracting mechanism is triggered Put.

Upon being activated, shrink trigger and can trigger contracting mechanism, so that by grouting socket button 216 from vertical bottom State is increased to vertically convex state.In the exemplary embodiment, stopper 210 and/or piston actuater 212 can include connecting To the coupling member shrinking trigger.Coupling member can include tether, auricle or other link mechanism.Coupling member can have There is suitable length, thus when stopper 210 is moved into the end of cylindrical portion 206（To inject controlling of doses Treat agent）, link mechanism's trigger latch, then start and shrink trigger.In a further exemplary embodiment, skin sensor foot The extension of 232 bottoms from shell 202 can start contraction trigger.

In the exemplary embodiment, contracting mechanism can include triggering upon being activated the administration of contracting mechanism and terminate to shrink Trigger.When the therapeutic agent of the treatment effective dose in Wearable automatic injection device 200 is injected into, administration can be started Terminate to shrink trigger.In the exemplary embodiment, administration end contraction trigger can include breech lock, for example, elastoplast Hook, it is released when therapeutic agent injection completes.Contracting mechanism can also include removing contraction trigger in advance, and it is being activated When trigger contracting mechanism.Automatic when removing Wearable from injection phase before being fully injected into the therapeutic agent for the treatment of effective dose During injection device 200, removing contraction trigger in advance can be activated.In the exemplary embodiment, remove contraction triggering in advance Device can include breech lock, for example, elastoplast hook, its quilt when removing Wearable automatic injection device 200 from injection phase Release.Contracting mechanism comes from injection phase in response to administration end contraction trigger and in response to removing contraction trigger in advance Automatically shrink injector assembly.

In the exemplary embodiment, grouting socket button 216 is increased to vertically convex position can lead to pierce through syringe needle 220 are bent upwards, and thus prevent from undesirably reusing puncture syringe needle and Wearable automatic injection device 200.

In the exemplary embodiment, Wearable automatic injection device 100（In Fig. 1）/200（In Fig. 2）Cylindrical portion Can be by pre-filled with any proper amount of therapeutic agent.In the exemplary embodiment, cylindrical portion 106 can be filled with about 0.1 milliliter and about 3.0 milliliters of volumes between, but the exemplary range of exemplary means not limited to this treatment volume.Treating Injected slurry volume is more than in the exemplary embodiment of the capacity of cylindrical portion of device, can arrange two or more cylinders in a device Shape partly to preserve the therapeutic agent of whole amount.Other parts in device can be configured to grouting socket from multiple tubulars Part projects therapeutic agent, to inject to patient.In a further exemplary embodiment, each include two of cylindrical portion or Multiple automated injection devices can be configured so that the therapeutic agent of injection whole amount.

In the exemplary embodiment, Wearable automatic injection device 100（In Fig. 1）/200（In Fig. 2）Can be used for The therapeutic agent of therapeutically effective amount is injected in the range of the time period of about 20 seconds to about 12 hours.Some other examples embodiments There is provided with the actuation means of rapid rate actuated cannula piston and system, to be injected in the patient therapeutic agent with rapid rate. Exemplary Rapid Implementation example can inject the therapeutic agent of about 0.5 milliliter to about 1 milliliter amount in about one second to about 20 seconds, but It is exemplary charge velocity not limited to this exemplary range.

Exemplary embodiment can provide the linear injection curve of therapeutic agent, so that charge velocity is substantially permanent in time Fixed.In some cases, linear injection curve can mitigate the sense of discomfort of patient.In the exemplary embodiment, can be once fast Speed injects therapeutic agent heavy dose ofly.

The charge velocity of therapeutic agent may rely on ambient temperature.At room temperature, that is, about 72 °F, the degree of accuracy of injection length Can be between about 3 percent and about 10.

The exemplary dimensions of exemplary means are described with reference to table 1-6.However, those of ordinary skill in the art should be understood that showing Example property size illustrating that property purpose and provide, and exemplary automated injection device is not limited to described illustrative dimension.

In the exemplary embodiment, Wearable automatic injection device can have about 4.37 inches exemplary lengths, The exemplary height of about 2.12 inches of exemplary width and about 1.25 inches.In the exemplary embodiment, cylindrical portion A diameter of about 1.470 inches, and the length of cylindrical portion is about 2.520 inches.Table 1-3 summarizes two kinds of exemplary types respectively The part length of exemplary means, width and height.

Table 1：The part length of exemplary means is summarized（Inch）

Element	Class1	Type 2
			Wall thickness	0.185	0.120
Partition	0.397	0.272
			Syringe needle	0.500	0.500
Cylindrical portion	2.520	2.520
			Propelling spring	0.470	0.322
Hydraulic connectors	0.113	0.113
			Wall thickness	0.185	0.120
Amount to	4.370	3.968

Table 2：The component width of exemplary means is summarized（Inch）

Element	Class1	Type 2
			Wall thickness	0.185	0.120
Grouting socket is locked	1.045	0.935
			Cylindrical portion width	0.470	0.470
Syringe is locked	0.235	0.235
			Wall thickness	0.185	0.120
Amount to	2.120	1.880

Table 3：The component height of exemplary means is summarized（Inch）

Element	Class1	Type 2
			Wall thickness	0.100	0.120
Needle cover	0.431	0.431
			Partition	0.400	0.350
Compressed height of spring	0.200	0.000
			Wall thickness	0.185	0.125
Amount to	1.316	1.026

In the exemplary embodiment, when producing, the diameter of cylindrical portion can increase about 0.125 from about 1.470 inches Inch, and when producing, the length of cylindrical portion can reduce about 0.732 inch from about 2.520 inches.Table 4-6 is total respectively The part length of exemplary means of two kinds of exemplary types of knot, width and height.

Table 4：The part length of exemplary means is summarized（Inch）

Element	Class1	Type 2
			Wall thickness	0.185	0.120
Partition	0.397	0.272
			Syringe needle	0.500	0.250
Cylindrical portion	2.520	1.788
			Propelling spring	0.470	0.322
Hydraulic connectors	0.113	0.113
			Wall thickness	0.185	0.120
Amount to	4.370	2.986

Table 5：The component width of exemplary means is summarized（Inch）

Element	Class1	Type 2
			Wall thickness	0.185	0.120
Grouting socket is locked	1.045	0.935
			Cylindrical portion width	0.470	0.595
Syringe is locked	0.235	0.235
			Wall thickness	0.185	0.120
Amount to	2.120	2.005

Table 6：The component height of exemplary means is summarized（Inch）

Element	Class1	Type 2
			Wall thickness	0.100	0.120
Needle cover	0.431	0.493
			Partition	0.400	0.350
Compressed height of spring	0.200	0.000
			Wall thickness	0.185	0.125
Amount to	1.316	1.088

Fig. 3 is the flow chart of the illustrative methods 300 assembling exemplary automated injection device 100.

In step 302, can sterilize and assemble injector assembly or injection cartridge module.

In step 304, can sterilize and assemble grouting socket button.It is included in the example in injection cartridge module in therapeutic agent Property embodiment in, grouting socket button can include and/or keep grouting socket, pierce through syringe needle and be arranged on puncture syringe needle and note Fluid passage between incoming interface.In the exemplary embodiment, can the injection to grouting socket button connect before assembly Mouth, puncture syringe needle and fluid passage carry out disinfection.In the exemplary embodiment, aseptic puncture needle cover（For example, paper tinsel, flexibility Or rigidity needle cover etc.）Can be used for covering and pierce through syringe needle and keep puncture syringe needle to be under aseptic condition.Aseptic puncture pin Head, aseptic puncture needle cover, aseptic grouting socket and aseptic grouting socket lid can provide sterile barrier with assembling Keep the fluid passage in grouting socket button aseptic during and after automated injection device.Therefore, in assembling automatic injection dress The inner surface in grouting socket button and fluid passage can be kept during and after putting to be under aseptic condition, such that it is able to Sterile manner injects sterile treatment agent.

In the another exemplary embodiment that therapeutic agent is included in injector assembly, grouting socket button can include And/or keep grouting socket and the fluid passage for injector assembly being connected to grouting socket.In this exemplary embodiment In, can before assembly the grouting socket and fluid passage of grouting socket button be carried out disinfection.In the exemplary embodiment, Sterility cover（For example, paper tinsel, flexibility or rigidity needle cover etc.）Can be used for covering grouting socket and to keep grouting socket to be in aseptic Under the conditions of.In the exemplary embodiment, grouting socket can also include sterile septum, and it is used for covering and keep partition aseptic Sterile septum lid cover.Aseptic grouting socket, aseptic grouting socket lid, aseptic partition and sterile septum lid can carry For sterile barrier to keep the fluid passage in grouting socket button aseptic during and after assembling automated injection device.Cause This, can keep the inner surface in grouting socket button and fluid passage to be in no during and after assembling automated injection device Under the conditions of bacterium, such that it is able to sterile treatment agent is injected with sterile manner.

In step 306, the aseptic cylindrical portion of injector assembly or injection cartridge module can be filled with patient to be implanted The sterile treatment agent of internal doses.In step 308, aseptic stopper can be placed in injector assembly or injection tube group Close end office in the cylindrical portion of part（Apart from grouting socket farther out）, the therapeutic agent of doses is sealed in cylindrical part In point.

It is included in the exemplary embodiment in injection cartridge module in therapeutic agent, the sterile septum being covered by sterile septum lid The far-end of the cylindrical portion of injection cartridge module can be arranged on（Nearer apart from grouting socket）.Aseptic stopper and sterile septum Jointly the sterile treatment agent of doses can be sealed in aseptic cylindrical portion.Aseptic cylindrical portion, aseptic stopper, no Bacterium partition and sterile septum lid can provide sterile barrier to keep injection tube group during and after assembling automated injection device Fluid passage in part is aseptic.Therefore, therapeutic agent is comprised with the sterile septum that covered by sterile septum lid by aseptic stopper In aseptic cylindrical portion, therapeutic agent can be kept aseptic during and after assembling automated injection device.

In the another exemplary embodiment that therapeutic agent is included in injector assembly, aseptic puncture syringe needle can be attached Distal portions to the cylindrical portion of injector assembly.In the exemplary embodiment, aseptic puncture needle skull（For example, paper tinsel, flexibility Or rigidity needle cover etc.）Can be used for covering and pierce through syringe needle and keep puncture syringe needle to be under aseptic condition.Pierce through needle cover The fluid passage being formed and be connected to by puncture syringe needle puncture syringe needle can also be kept aseptic.Aseptic cylindrical portion, asepsis plug Sub, aseptic puncture syringe needle and aseptic puncture needle cover can provide sterile barrier, to keep the fluid in injector assembly Passage is aseptic.Therefore, by aseptic stopper with by the aseptic aseptic puncture syringe needle piercing through syringe needle covering, therapeutic agent is included in no In bacterium cylindrical portion, therapeutic agent can be kept aseptic during and after assembling automated injection device.

Using above-mentioned example embodiment, injector assembly or the cylindrical portion of injection cartridge module and grouting socket is kept to press Aseptic with the fluid passage betwixt extending in button.Keep aseptic during and after assembling automated injection device, so that Device can be used for executing the aseptic injection of therapeutic agent.In this way, exemplary embodiment guaranteed in the injection sterile treatment agent phase Between therapeutic agent using or along from injector assembly or injection cartridge module by grouting socket button reach patient sterile fluid Passage.

In the exemplary embodiment, the remainder of Wearable automatic injection device can be assembled in ambient non-sterile Part, the fluid passage in holding meanss is aseptic simultaneously.In a further exemplary embodiment, can be before assembly to remainder Carry out disinfection.

In step 310, can be by non-sterile piston actuater（For example, biasing mechanism）Be inserted in after stopper, for Injection state actuated plug is to project therapeutic agent from cylindrical portion.

In step 312, can be by shell non-sterile to injector assembly or injection cartridge module insertion.Shell can be with one Individual or multiple other non-sterile parts（For example, adhesive layer, protecting film, skin sensor foot etc.）It is pre-assembled in together.

In step 314, can be by grouting socket button（Have in the exemplary embodiment closing sterile fluid passage and Aseptic grouting socket）Insert in non-sterile shell.

In step 316, if necessary the automated injection device of assembling can be placed in outer package, and permissible Commercial packing is carried out to sell to it.In the exemplary embodiment, a part for device can be attached to the interior table of packaging In the part in face.

Fig. 4 is the flow chart of the illustrative methods 400 using exemplary automated injection device.Before the use, generally may be used So that the packaged and pre-filled Wearable automatic injection device with therapeutic agent to be stored in cold storage plant.In step 402, The automated injection device of packaging can be taken out from cold storage plant.In step 404, can be from the bag of Wearable automatic injection device This device is taken out in dress and any wrappage, and at room temperature or logical by for example putting the Wearable device removing packaging Cross heating Wearable device, make device be warming up to room temperature.In step 406, patient can be by controlling in crust of the device Treat agent observation window and confirm that cylindrical portion comprises a certain amount of therapeutic agent, and can also confirm that the net of therapeutic agent if necessary Degree.

In step 408, the injection phase on patient body can be selected and make this position be ready for injecting therapeutic agent. In step 410, patient uses Wearable automatic injection device to inject in the patient therapeutic agent at injection phase.Tie below Close Fig. 5 and describe the step being usually directed in step 410.In step 412, after injection therapeutic agent, can remove from patient can Worn type automated injection device and being abandoned in an appropriate manner.

Fig. 5 be using exemplary automated injection device by the injection of the therapeutic agent of therapeutically effective amount exemplary side in the patient The flow chart of method 500.Illustrative methods 500 are the detailed outline of the step 410 in Fig. 4.

In step 502, patient removes the protecting film of the adhesive layer covering and protecting Wearable automatic injection device.Showing In example property embodiment, a part of inner surface that can be attached to device package of protecting film, and withdrawing device can from the package Automatically to remove protecting film.In some exemplary embodiments, remove protecting film also to remove grouting socket lid, pierce through syringe needle Partition lid in lid and syringe or injection tube retainer.

In step 504, the patient contacting portions with the Wearable automatic injection device of adhesive layer are applied to by patient Injection phase on patient body（Or the medicated clothing around injection phase）, so that device controlling in injection treatment effective dose It is reliably held on injection phase during treating agent.

In step 506, once Wearable automatic injection device is attached to injection phase, injection just can be connect by patient Mouth button is pressed into, from the vertically convex position of pre-implant state, the vertical lower position being in shell in injection state.Perpendicular Directly convex position, the end-contraction of the grouting socket button of supporting grouting socket and is not exposed to outer side in shell. When pressed, the end of the grouting socket button of supporting grouting socket edge in shell point-blank or rotatably moves down, So that occurring in breach from shell for the grouting socket and being exposed to outer side.This allows grouting socket to pass through for example to pierce Enter the suitable depth of patient body and couple with patient body, so that injection therapeutic agent.Grouting socket button in shell to Lower movement can be along straight line（That is, move straight down）Or rotation（That is, circumferentially move around pivotal point）.

In the exemplary embodiment, grouting socket button can manually be pressed down on by grouting socket button by patient It is pressed in shell.In a further exemplary embodiment, patient can start injection trigger, for example, positioned at conventional accessible Position（Such as cover top portion）Trigger button, this makes injection trigger that grouting socket button to be automatically pressed in shell, And so that grouting socket is coupled with the body of patient by for example piercing through the body of patient.In the exemplary embodiment, press Pressure trigger button can discharge the breech lock in injection trigger, and this allows spring biased downward grouting socket in shell to press Button.The same movement of grouting socket button can make grouting socket insertion or be applied to injection phase on patient body to suitable Depth.

In step 508, press grouting socket button and can trigger syringe or injection tube actuator, syringe or injection tube Actuator by injector assembly or injects cartridge module in shell or with respect to shell（More particularly cylindrical portion）From contraction Position（In this position, the far-end of injector assembly or injection cartridge module is separated with grouting socket button）Move forward to stretching, extension Position（In this position, the far-end of injector assembly or injection cartridge module is adjacent with grouting socket button and/or contacts）.Another In exemplary embodiment, do not pass through to press grouting socket button, but touching of such as trigger button form is started by patient Send out device, to trigger syringe or injection tube actuator.In the exemplary embodiment, injector assembly or injection cartridge module are towards note The movement of incoming interface button can make puncture needle pierces partition.

In step 510, piston actuater can weaken the static friction between stopper and the inwall of cylindrical portion（I.e. static friction Power）And so that stopper is moved towards the puncture needle forward in grouting socket button, to inject therapeutic agent via grouting socket.Live Plug actuator can overcome in one step stopper stiction and in later step actuated plug, or plunger actuation Device can overcome stopper stiction actuated plug simultaneously.The movement of stopper can make therapeutic agent be released by piercing through syringe needle To in grouting socket, and thus therapeutic agent can be injected in the patient.

In the exemplary embodiment, injector assembly or injection advance forward in shell for the cartridge module and stopper are in cylinder Shape partly in forward advance can occur in different steps.In another embodiment, injector assembly or injection tube group In advancing forward in shell and stopper can in same step in the advance forward in cylindrical portion part occur, for example same Shi Fasheng.

The charge velocity of therapeutic agent may rely on the characteristic of piston actuater.Piston actuater can take some examples The form of property embodiment.In some exemplary embodiments, piston actuater can adopt energy stores and release device, example As biasing mechanism（Including but not limited to, one or more springs, such as helical spring or helical compression spring）, compressed gas Body, chemical gas generator（Such as expanded foam）, osmotic pressure, hydrogel expand etc..Damping or controlling organization（Including but not It is limited to viscous damper or eacapement）Can be used for energy absorption（The energy of such as initially release）And in piston actuater More controlled energy release is provided during releasing energy.The flow restriction in fluid passage between grouting socket and stopper Device can be used for the charge velocity of further adjustment for the treatment of agent, and for example, piston actuater gives unfettered via working fluid Spring force.It is thereby possible to select suitable piston actuater and suitable controlling organization come so that patient will not or substantially not May feel that the controllable rate of any burn feeling（For example, bolus）Injection therapeutic agent.

In the exemplary embodiment, pressing grouting socket button can make contracting mechanism be ready for applying, in injection Rear injection state afterwards, when activated this contracting mechanism grouting socket button is retracted in shell 102.

In step 512, when injecting the therapeutic agent for the treatment of effective dose, stopper and/or piston actuater can start receipts The administration of contracting mechanism terminates to shrink trigger.Stopper and/or piston actuater can include being connected to administration end contraction triggering The coupling member of device.Coupling member can include tether, auricle or other link mechanism.Coupling member can have properly long Degree so that when stopper be moved into injector assembly or injection cartridge module end when（So that the treatment of injection doses Agent）, coupling member triggering then start shrink trigger breech lock.

In step 514, once start administration to terminate to shrink trigger, contracting mechanism just can by grouting socket button upwards It is retracted to inside the shell and away from patient contacting portions, so that injector assembly or injection cartridge module inject shape after entering State.In the exemplary embodiment, grouting socket button from injection state to rear injection state mobile generation audible sounds, for example " click " sound, this provides the therapeutic agent audible indication that injection completes.Once shrinking, grouting socket button just projects into outside shell Side, this provides the state of Wearable automatic injection device（For example, therapeutic agent injection completes）Visual instruction or device be in Inject the visual instruction of state afterwards.

If however, removing Wearable dress from patient body before the therapeutic agent injection for the treatment of effective dose completes Put, then skin sensor foot extend to outer side and start contracting mechanism remove contraction trigger in advance.Once Remove contraction trigger in advance to be activated, contracting mechanism just stretches upwards grouting socket button so as to away from patient in shell Contact portion, so that injector assembly or injection cartridge module inject state after entering.In the exemplary embodiment, when controlling The therapeutic agent for the treatment of effective dose injects before completing when patient body removes Wearable device, and piston actuater can be in cylinder Shape is partly middle to be continued to move along towards puncture syringe needle.

In step 516, when deflated, grouting socket locking mechanism is engaged with grouting socket, to prevent grouting socket in note Stretch again after entering therapeutic agent, thus providing acupuncture to protect.Grouting socket lock be once engage can be just to prevent injection from connecing Mouth projects into the component of outer side, and grouting socket lock may be located at close grouting socket in shell.Exemplary injection Interface lock can include but is not limited to plastic plate, metallic plate, clip etc..

Fig. 6 A-6C diagram is suitable to grouting socket inserts along straight line or is applied to the Wearable automatic injection device of patient 600 exemplary embodiment.By inserting along straight line, the end of the injection cartridge module of supporting grouting socket is automatic in Wearable Decline along straight line in the shell of injection device, thus by grouting socket insertion or being applied to patient.More specifically, at Fig. 6 A diagram In pre-implant state（For example, packaged）Exemplary Wearable device；Fig. 6 B diagram is in injection state（Just will control When before treating agent injection in the patient, by therapeutic agent injection in the patient or just by after therapeutic agent injection in the patient）'s Exemplary Wearable device；And Fig. 6 C diagram is in and has completed therapeutic agent injection in the patient or in therapeutic agent injection Remove the exemplary Wearable device of the rear injection state of device from patient before completing.Some in figures in Fig. 6 A-6C, Grouting socket can be depicted as single injection needle.However, exemplary grouting socket be not limited to illustrative shown in Fig. 6 A-6C Embodiment.

Wearable automatic injection device 600 includes the shell 635 for housing injection of therapeutic agent cartridge module 610, treatment The therapeutic agent that cartridge module 610 comprises the doses in the patient for injection is injected in agent.In the exemplary embodiment, therapeutic agent Injection cartridge module 610 can be provided with one or more ribs, and the inner side of shell 635 can be provided with when injection cartridge module One or more grooves or the groove of smooth passage are provided for injecting the rib of cartridge module 610 when moving in shell 635.In note One or more ribs on shooting cylinder assembly 610 outside can take the form of the convex line on injection cartridge module 610.In shell One or more grooves on 635 inner side or groove U-shaped can be taken recessed or trough shaped pipeline form.Groove or groove Top can be opening so that rib can slide in and out the top of groove or groove.Shown in Fig. 6 A-C Along along the embodiment of straight line insertion, rib and recess/grooves can be flat tube.Being rotatably inserted into shown in Fig. 7 A-7C In embodiment, rib and recess/grooves may be about center of rotation（Inject the pivotal point of cartridge module 610）The pipe of bending Road.

In a further exemplary embodiment, the outside of injection cartridge module 610 can not have any rib, and shell 635 inner side can not have any groove or groove.

Shell 635 preferably has elongated configuration, but those of ordinary skill in the art should be understood that shell 635 can have For housing any suitably sized, shape and the configuration of cylindrical portion, cylindrical portion is used for preserving the therapeutic agent of doses And grouting socket can be connected to, so that therapeutic agent is injected in the patient.Shell 635 can be by any suitable material shape Become, including but not limited to plastics and other known material.In another embodiment, injection of therapeutic agent cylinder 610 can by be suitable to into Any compatible material of row sterilization is formed, and it includes but is not limited to glass and other known material.

Shell 635 includes the adhesive layer 640 placed along the patient contacting portions of shell 635, the patient contacting portion of shell 635 Divide the medicated clothing being arranged to neighbouring patient skin or patient.In some exemplary embodiments, adhesive layer 640 is configured to be located at On the skin of patient, thus shell 635 is attached to patient to inject therapeutic agent.Adhesive layer 640 includes non-sticky removing mechanism 645, for example do not have sticking auricle.Patient can catch and pull non-sticky removing mechanism 645, with from the skin of patient or clothing Adhesive layer 640 is removed on clothes, and then removes Wearable automatic injection device 600.

Before using Wearable automatic injection device 600, for instance in pre-implant state, adhesive layer 640 is protected Film 650 covers, and it keeps the bond property of adhesive layer 640.Protecting film 650 can include removing mechanism 655, such as auricle, suffers from Person can catch and pull removing mechanism 655 to remove protecting film 650 from adhesive layer 640.So expose adhesive layer 640 so that Patient can by by that side with adhesive layer 640 be placed on skin or medicated clothing by shell 635 be attached to his or she Skin or this part clothes on.

In the exemplary embodiment, protecting film 650（In fig. 6）/750（In fig. 7）Can include being connected to piston Actuator 630（In fig. 6）/730（In fig. 7）Coupling member.Coupling member can include tether, auricle or other even Knot mechanism.When removing protecting film 650（In fig. 6）/750（In fig. 7）When, protecting film 650（In fig. 6）/750（In figure In 7A）Coupling member reduce stopper 615（In fig. 6）/715（In fig. 7）With cylinder 605（In fig. 6）/705（In figure In 7A）Inwall between static friction, and trigger piston actuater 630（In fig. 6）/730（In fig. 7）.

Injection of therapeutic agent cartridge module 610 can include the treatment for preserving treatment effective dose in the patient to be implanted The hollow barrel-type part 605 of agent.Shown cylindrical portion 605 is general cylindrical shape, but those of ordinary skill in the art should This understands, cylindrical portion 605 can have any suitable shape or configuration.The therapeutic agent of doses is sealed by stopper 615 In cylindrical portion 605.Injection of therapeutic agent cartridge module 610 can also include being connected to or be connected to cylindrical portion 605 and with The grouting socket 625 that cylindrical portion 605 is in fluid communication, can be via grouting socket by applying pressure therapy agent to stopper 615 625 injections.

In some exemplary embodiments, grouting socket 625 can include having and be adapted to pierce through patient skin and controlled with injecting Treat any suitably sized, shape of agent and one or more injection needles of configuration, and be not limited to illustrative embodiment.? In exemplary embodiment, grouting socket 625 can include single injection needle（Illustrated by the solid line in Fig. 6 A-6C）.Another In exemplary embodiment, grouting socket 625 can include two or more injection needles（By the volume shown in phantom in Fig. 6 A-6C Outer syringe needle）.In some other examples embodiments, grouting socket 625 can include noting for the local executing therapeutic agent The needleless liner entering and/or needleless paster.

The suitable syringe needle that can be used for exemplary grouting socket can have and is configured to or is chosen as control needed for offer is suitable to The length of the injection depth treated.Subcutaneous injection generally pierces about six to ten millimeters of skin.In the exemplary embodiment, exemplary note Penetrate syringe needle to have the length of about 12mm and skin can be injected to the depth of about 7mm.In other exemplary embodiments of the invention, Exemplary ejection syringe needle can have the length being suitable to dermal treatment, other subcutaneous therapy or muscle treatment.Suitable syringe needle can Patient is felt to be down to by the material flow needed for have the wall thickness being adapted to provide for enough mechanical strengths, to be adapted to allow for simultaneously Minimum diameter and be suitable to required treatment and feel to be down to minimum tip geometry by patient simultaneously.

In the case of pharmaceutically acceptable, exemplary ejection syringe needle can be coated as needed, patient is felt to be down to Low.Grouting socket 625 can be capped and pass through grouting socket lid 620（For example, rigid needle shield, flexible needle housing or both）Keep It is under the conditions of being uninfected by.

In exemplary embodiment shown in Fig. 6 A-6C, the longitudinal direction substantially with Wearable device 600 for the grouting socket 625 Axis projection at a right angle.In the exemplary embodiment, cylindrical portion 605 include with the longitudinal axis of device 600 be in substantially The elbow 607 squarely extending.In this embodiment, grouting socket 625 is connected to elbow 607.

Wearable automatic injection device 600 can include piston actuater 630, and piston actuater 630 is used for direction and controls Treat far-end optionally actuated plug 615 forward that cartridge module 610 is injected in agent, will be contained in the treatment in cylindrical portion 605 The therapeutic agent of effective dose injects in the patient.Piston actuater 630 can adopt energy stores and controlled energy relieving mechanism Carry out actuated plug 615.In the exemplary embodiment, piston actuater 630 can include biasing mechanism, such as spring, and it is in note Shrink before entering and be released with activated forwards stopper 615 in cylindrical portion 605 in injection period.Real in another exemplary Apply in example, piston actuater 630 can include chemical gas generator, such as expanded foam, it is in non-swollen before injection The swollen stage and injection period expand to cause forward towards the far-end of injection of therapeutic agent cartridge module 610 in cylindrical portion 605 Dynamic stopper 615.In other exemplary embodiments of the invention, piston actuater 630 can adopt compressed gas, osmotic pressure, hydrogel Expand etc..Damping mechanism can be used for energy absorption（The energy of such as initial release）And pass through piston in energy deenergized period Actuator 630（In fig. 6）/730（In fig. 7）Controlled energy release is provided.Positioned at grouting socket and stopper 615（? In Fig. 6 A）/715（In fig. 7）Between fluid passage in flow restrictor can be used for the note of further adjustment for the treatment of agent Enter speed, for example, piston actuater 630（In fig. 6）/730（In fig. 7）Give free spring force.

In the exemplary embodiment, piston actuater 630 can in cylindrical portion 605 with constant linear motion forward Advance.Any amount of mechanism inside or outside Wearable automatic injection device 600 may be used to provide constant straight Line moves, and described mechanism is including but not limited to connected to the stepping motor of gear train assembly.

Stopper 615（In fig. 6）/715（In fig. 7）And/or piston actuater 630（In fig. 6）/730（In figure In 7A）Can include being connected to the coupling member shrinking trigger.Coupling member can include tether, auricle or other link structure Part.Coupling member can have suitable length so that working as stopper 615（In fig. 6）/715（In fig. 7）It is moved into During the end of injection cartridge module 610（So that the therapeutic agent of injection doses）, coupling member triggering starts then shrinks triggering The breech lock of device.

Referring now to Fig. 6 C, in the exemplary embodiment, shell 635 includes skin sensor foot 660, and it is to house outside The partly lower or interior structure of the close injection phase of shell 635.Injection therapeutic agent before and injection period, skin sensor foot In a part for 660 downsides being maintained at shell 635 or form this part.When Wearable automatic injection device 600 is attached To injection phase and when being activated, skin sensor foot 660 can move freely, but is constrained by injection phase.When from note When entering position and removing Wearable automatic injection device 600, no matter whether therapeutic agent injects completes, and skin sensor foot 660 is not Constrained again, and extend and project into outside the edge of shell 635.This then starts and removes contraction trigger.

Fig. 6 A diagram is in pre-implant state（For example packaged and preparation uses or prepares packaging）Wearable automatic Injection device 600.Device 600 can include can be pre-filled and/or pre-filled injector assembly or injection cartridge module.Showing In example property embodiment, in pre-implant state, injector assembly or injection cartridge module may be at punctured position in case using.Pre- Injection state, injection of therapeutic agent cartridge module 610 is positioned partially at the erect position away from injection phase in shell 635, and Grouting socket 625 is contracted in shell 635.Indicate the visual finger that patient's Wearable automatic injection device 600 is operated Show the part that can include projecting into the injection of therapeutic agent cartridge module 610 outside shell 635 in pre-implant state.Cylindrical portion 605 therapeutic agents comprising doses, described therapeutic agent is comprised in restriction between the wall of cylindrical portion 605 and stopper 615 In inner space.In an embodiment, piston actuater 630 storage energy.

Fig. 6 B diagram is in injection state（Prepare to inject, in injection process or just in injection treatment effective dose Therapeutic agent after）Wearable automatic injection device 600, wherein, injection of therapeutic agent cartridge module 610 is in recessed location. In recessed location, injection of therapeutic agent cartridge module 610 is located in shell 635 at the recessed location of injection phase, and injects Interface 625 is projected into outside shell 635 by the breach in shell 635, such that it is able to pierce body at injection phase.In note Enter in state, injection of therapeutic agent cartridge module 610 not projecting to outside shell 635, with to patient provide Wearable automatic injection The visual instruction that device 600 is operating.The energy of piston actuater 630 its storage of release is with actuated plug 615.Plunger actuation This collaborative grouting socket 625 that is moved through of device 630 and stopper 615 projects the therapeutic agent in cylindrical portion 605.

Fig. 6 C diagram injects the Wearable automatic injection device 600 of state after being in, for example, in injection treatment effective agent Wearable automatic injection device is removed from patient after the therapeutic agent of amount or before the therapeutic agent of injection treatment effective dose After 600, wherein, injection of therapeutic agent cartridge module 610 is in punctured position.In punctured position, injection of therapeutic agent cartridge module 610 The erect position away from injection phase in shell 635, and grouting socket 625 is contracted in shell 635.Injection of therapeutic agent cylinder A part for assembly 610 projects into the outside of shell 635, to provide Wearable automatic injection device assembly 600 not to patient Operated（State is injected after being in）Visual instruction.Cylindrical portion 605 can be not filled with therapeutic agent, and piston causes Dynamic device 630 can no longer storage energy.

Shell 635 includes making injection of therapeutic agent cartridge module 610 from injection state（Recessed location shown in Fig. 6 B）Automatically rise Up to inject state afterwards（Punctured position shown in Fig. 6 C）Contracting mechanism.In the exemplary embodiment, contracting mechanism can wrap Include biasing mechanism, such as spring, it will inject cartridge module and bias away from injection phase when contracting mechanism is triggered.

The administration that contracting mechanism includes triggering upon being activated contracting mechanism terminates to shrink trigger.When Wearable is automatic When the therapeutic agent of the treatment effective dose in injection device is injected into, starts administration and terminate to shrink trigger.In exemplary enforcement In example, administration terminates contraction trigger and can include breech lock, for example, elastoplast hook, it is released when therapeutic agent injection completes Put.Contracting mechanism also includes removing contraction trigger in advance, and it triggers contracting mechanism when being activated.When being fully injected into treatment Before the therapeutic agent of effective dose when injection phase removes Wearable automatic injection device, remove contraction trigger quilt in advance Start.In the exemplary embodiment, remove contraction trigger in advance and can include breech lock, for example, elastoplast hook, it is from note Enter position and remove and be released during Wearable automatic injection device 600.Contracting mechanism terminates to shrink trigger simultaneously in response to administration And automatically to shrink injector assembly from injection phase in response to removing contraction trigger in advance.

Fig. 7 A-7C diagram is suitable to grouting socket is rotatably inserted into or is applied to the Wearable automatic injection device of patient 700 exemplary embodiment.When being rotatably inserted into, the end of the injection of therapeutic agent cartridge module 710 of supporting grouting socket 725 is to revolve The mode that turns declines around pivotal point to insert grouting socket 725 or to be applied to patient.Grouting socket 725 can be configured to On skin, in skin or by skin, therapeutic agent is injected into and any requires depth.More specifically, Fig. 7 A diagram is in pre-implant The exemplary Wearable device of state, for example, be packaged with the grouting socket of pre-filled bending and the cylindrical part preserving therapeutic agent Point；Fig. 7 B diagram is in injection state（Just by therapeutic agent injection in the patient before, by therapeutic agent injection in the patient when Or just by after therapeutic agent injection in the patient）Exemplary Wearable device；And Fig. 7 C diagram is in therapeutic agent Rear injection state after patient removes device is exemplary after injection in the patient or before therapeutic agent injection completes Wearable device.Some in figures in Fig. 7 A-7C, grouting socket can be depicted as single injection needle.However, example Property grouting socket is not limited to the illustrative embodiment shown in Fig. 7 A-7C.

Injection of therapeutic agent cartridge module 710 can be rotatably moved around the pivotal point 765 in shell in shell 735. In the exemplary embodiment, the outside of injection of therapeutic agent cartridge module 710 can be provided with one or more ribs, and shell 735 inner side can be provided with one or more grooves or groove, under various regimes, when injection tube moves in shell 735 When, described groove or groove provide passage for the rib of injection tube 710.In a further exemplary embodiment, inject cartridge module 710 Outside there is no rib, and the inner side of shell 735 does not have groove or groove.

When injection of therapeutic agent cartridge module 710 is recessed in shell 735, injection of therapeutic agent cartridge module 710 is around pivotal point 765 rotatably move down, so that grouting socket 725 becomes to be exposed to and pierces patient skin.In exemplary enforcement In example, grouting socket 725 can include single injection needle（Illustrated by the solid line in Fig. 7 A-7C）.Implement in another exemplary In example, grouting socket 725 can include two or more injection needles（By the shown in phantom extra syringe needle in Fig. 7 A-7C）. In some other exemplary embodiments, grouting socket 725 can include the needleless being locally implanted for executing therapeutic agent Liner and/or needleless paster.

In exemplary embodiment shown in Fig. 7 A-7C, grouting socket 725 enters patient skin with the Fructus Gleditsia acupuncture offseting 90 °.Class As, when injection of therapeutic agent cartridge module 710 shrinks, injection of therapeutic agent cartridge module 710 is around pivotal point 765 rotatably upwards Mobile, so that grouting socket 725 is contracted in shell 735.Realize this rotary motion of injection of therapeutic agent cartridge module 710 Mechanism can the required mechanism of straight line insertion than Fig. 6 A-6C simpler and firmer.

In the exemplary embodiment, grouting socket 725 is bending, and its radius is by pivotal point 765 and indulging along shell 735 Limit to axis from grouting socket 725 to the distance of pivotal point 765.The bending of grouting socket 725 increases the application grouting socket phase Between patient comfort.For example, in the exemplary embodiment, the bending of grouting socket 725 increases exemplary grouting socket The patient comfort of one or more injection needle period inserted into the patient.Include one or more notes in grouting socket 725 Penetrate in the exemplary embodiment of syringe needle, grouting socket 725 can with the sharp needle tip closest to pivotal point 765 be preferentially Guiding.

Describe similar with the feature shown in Fig. 6 A-6C feature in Fig. 7 A-7C above in association with Fig. 6 A-6C.

In the exemplary embodiment, the injection of therapeutic agent cartridge module 610 and 720 of Fig. 6 A-6C and Fig. 7 A-7C respectively can be pre- It is filled with the therapeutic agent of any amount, for example, treatment antibody.In the exemplary embodiment, injection cartridge module 610 and 720 can be pre- It is filled with about 0.1 to about 3.0 milliliter of amount, but exemplary ejection cartridge module is not limited to these Exemplary amounts.In another example Property embodiment in, injection cartridge module 610 and 720 can be pre-filled with up to about 1 milliliter of amount.

In the exemplary embodiment, Wearable automatic injection device 600（In fig. 6）/700（In fig. 7）Permissible For injecting the therapeutic agent for the treatment of effective dose in the range of the time period of about 20 seconds to about 12 hours.In exemplary enforcement In example, in the injection length between about five minutes and about 30 minutes, therapeutic agent can be injected with fixed rate.Wearable Automated injection device 600（In fig. 6）/700（In fig. 7）Inject a certain amount for the treatment of with can be used for bolus Agent.

The charge velocity of therapeutic agent may rely on ambient temperature.At room temperature, that is, about 72 °F, the degree of accuracy of injection length Can be between about 3 percent and about 10.

Fig. 8 is the flow chart of the illustrative methods 800 assembling exemplary Wearable automatic injection device 600 or 700.

In step 805, to the cylindrical portion 605/705 of injection cartridge module, grouting socket 625/725 and grouting socket lid 620/720 carries out disinfection.In step 810, cylindrical portion 605/705 is by pre-filled with doses in the patient to be implanted Sterile treatment agent.In step 815, aseptic stopper 615/715 is placed in cylindrical portion 605/705, therapeutic agent is sealed In cylindrical portion 605/705.By aseptic cylindrical portion 605/705, aseptic stopper 615/715, grouting socket 625/725 With cap assemblies 620/720, therapeutic agent is included in Wearable automatic injection device 600 or 700, provides in the assembling device phase Between and keep the aseptic sterile barrier in fluid passage of therapeutic agent afterwards.

In the exemplary embodiment, after cylindrical portion 605/705 is filled with therapeutic agent, can be in ambient non-sterile The remainder of middle assembling Wearable automatic injection device, the fluid passage in holding meanss is aseptic simultaneously.In another example In property embodiment, the remainder of Wearable automatic injection device can be assembled in gnotobasiss.

In step 820, aseptic piston actuater 630/730 is inserted in injection of therapeutic agent cartridge module 610/710 After stopper 615/715, in injection state actuated plug, to project therapeutic agent from cylindrical portion.

In step 825, injection of therapeutic agent cartridge module 610/710 is inserted in sterile enclosure 635/735.Shell 635/735 Pre-assembled can there are one or more of the other sterile components, for example, adhesive layer 640/740, protecting film 650/750, skin sensing Device foot 660/760.

In step 830, if necessary, the Wearable automatic injection device 600/700 of assembling can be disposed outside In packaging, afterwards commercial packing is carried out to sell to it.In the exemplary embodiment, a part of of device can be attached to bag In a part for inner surface for dress.

Fig. 9 is the flow chart of the illustrative methods 900 using exemplary Wearable automatic injection device 600 or 700.? Using before, generally the packaged and pre-filled Wearable automatic injection device 600/700 with therapeutic agent is stored in cold Hide in device.In step 905, take out the Wearable automatic injection device 600/700 of packaging from cold storage plant.In step 910, Take out this device from the packaging of Wearable automatic injection device 600/700 and any wrappage, and by for example going Except the Wearable device of packaging is put at room temperature or by heating Wearable device, device is made to be warming up to room temperature.In step 915, patient is by confirming in Wearable device 600/700 positioned at the therapeutic agent observation window in the shell of Wearable device Injection of therapeutic agent cartridge module 610/710 includes a certain amount of therapeutic agent, and can also confirm that the net of therapeutic agent if necessary Degree.In step 920, select the injection phase on patient body and make this position be ready for injecting therapeutic agent.In step 925, patient uses Wearable automatic injection device 600/700 that therapeutic agent is injected the injection phase with patient.Tie below Close Figure 10 and describe the step being usually directed in step 920.In step 930, remove Wearable automatic injection device from patient After 600/700, abandon the Wearable automatic injection device 600/700 removing in an appropriate manner.

Figure 10 is to be injected the therapeutic agent of therapeutically effective amount using exemplary Wearable automatic injection device 600 or 700 The flow chart of illustrative methods 1000 in the patient.Illustrative methods 1000 are the detailed outline of the step 920 in Fig. 9.? Step 1005, patient removes the protecting film of the adhesive layer 640/740 covering and comprising Wearable automatic injection device 600/700 650/750.In the exemplary embodiment, a part of inner surface that can be attached to packaging of protecting film, and take from the package Go out device and can automatically remove protecting film.In some exemplary embodiments, remove protecting film 650/750 and also can remove lid group Part 620/720 and exposing for by therapeutic agent injection grouting socket 625/725 in the patient.In some exemplary embodiments In, remove protecting film 650/750 and also weaken the static friction between stopper 615/715 and the inwall of cylindrical portion 605/705（I.e. quiet Frictional force）And trigger piston actuater 630/730.In the exemplary embodiment, protecting film 650/750 can include being connected to The coupling member of piston actuater 630/730.Coupling member can include tether, auricle or other link mechanism.Work as protecting film 650/750 when being removed, and the coupling member of protecting film 650/750 reduces the inwall of stopper 615/715 and cylindrical portion 605/705 Between static friction, and trigger piston actuater 630/730.

In step 1010, patient will have the patient of the Wearable automatic injection device 600/700 of adhesive layer 640/740 Contact portion is applied to injection phase（Or the medicated clothing around injection phase）, so that Wearable device has in injection treatment It is reliably held on injection phase during the therapeutic agent of effect dosage.

In step 1015, once Wearable automatic injection device 600/700 is attached to injection phase, injection of therapeutic agent Cartridge module 610/710 is pressed against from the ready position of pre-implant state and is in shell 635/735 injection state Recessed location.In ready position, support the end of the injection of therapeutic agent cartridge module 610/710 of grouting socket 625/725 It is contracted in shell 635/735 and be not exposed to outer side.When pressed, support the treatment of grouting socket 625/725 The end that cartridge module 610/710 is injected in agent point-blank or rotatably moves down on edge in shell 635/735, so that injection Breach from shell 635/735 for the interface 625/725 occurs and exposes.This allows grouting socket 625/725 to pierce patient body Suitable depth, so that injection therapeutic agent.Injection of therapeutic agent cartridge module 610/710 moving down in shell 635/735 can To be along straight line（That is, move straight down）Or rotation（That is, circumferentially move around pivotal point）.At Fig. 6 B and 7B diagram In injection state and injection of therapeutic agent cartridge module 610/710 is pressed against in shell 635/735 after execution step 1015 Wearable automatic injection device 600 and 700 exemplary embodiment.

In the exemplary embodiment, manually push down on injection of therapeutic agent cartridge module 610/710 by patient will treat Agent injection cartridge module 610/710 is pressed in shell 635/735.In a further exemplary embodiment, patient can start insertion Trigger, for example, positioned at conventional accessible position（The top of such as shell 635/735）Trigger button, this make insertion trigger Injection of therapeutic agent cartridge module 610/710 is automatically pressed in shell 635/735 device, and then makes grouting socket 625/725 Pierce through patient body.In the exemplary embodiment, squeezing trigger button can discharge the breech lock in trigger, and this allows spring Biased downward injection cartridge module 610/710 in shell 635/735.The same movement of injection cartridge module 610/710 can make note Incoming interface 625/725 inserts or is applied to injection phase with patient to suitable depth.

In the exemplary embodiment, Therapeutic pressing agent injection cartridge module 610/710 can trigger piston actuater 630/730 makes Obtain stopper 615/715 to start to move, synergistically to inject in the patient the therapeutic agent for the treatment of effective dose.Therapeutic pressing agent is noted Shooting cylinder assembly 610/710 makes piston actuater 630/730 weaken between stopper 615/715 and the inwall of cylindrical portion 605/705 Static friction（I.e. stiction）And make stopper 615/715 towards the grouting socket in injection of therapeutic agent cartridge module 610/710 625/725 forward movement, to inject therapeutic agent via grouting socket 625/725.Piston actuater 630/730 can walk at one Overcome in rapid stopper stiction and in later step actuated plug, or piston actuater 630/730 can simultaneously gram Take stopper stiction actuated plug.In a further exemplary embodiment, it is not through Therapeutic pressing agent injection tube, but logical Cross patient and start the injection trigger of such as trigger button form triggering piston actuater 630/730.

The charge velocity of therapeutic agent may rely on the characteristic of piston actuater 630/730.Piston actuater 630/730 can In the form of taking some exemplary embodiments.In some exemplary embodiments, piston actuater 630/730 can adopt energy Amount storage and release device, for example, biasing mechanism（Such as spring）, compressed gas, chemical gas generator（Such as expand bubble Foam）, osmotic pressure, hydrogel expand etc..Damping mechanism can be used for energy absorption（The energy of such as initially release）And Piston actuater 630/730 provides more controlled energy release during releasing energy.Positioned at grouting socket and stopper 615/715 it Between traffic channel in flow restrictor can be used for the charge velocity of further adjustment for the treatment of agent, for example, piston actuater 630/730 gives free spring force.It is thereby possible to select suitable piston actuater 630/730 and suitable flow Limiter comes so that patient or will not feel as the controllable rate of any burn feeling substantially（For example, bolus） Injection therapeutic agent.

In the exemplary embodiment, Therapeutic pressing agent injection cartridge module 610/710 also makes contracting mechanism be ready for answering With injection of therapeutic agent cartridge module 610/710 is retracted in shell 635/735 this contracting mechanism when activated.

In step 1020, injection of therapeutic agent cartridge module 610/710 injects the punctured bit of state after recessed location is retracted to Put, so that it projects into outside shell 635/735, and grouting socket 625/725 is contracted in shell 635/735 or is subject to skin Skin sensor foot 660/760 is protected or two kinds of situations occur simultaneously.Fig. 6 C and 7C diagram is respectively at receipts after step 1020 Condense the exemplary embodiment of the automated injection device 600 and 700 put.When inject treatment effective dose therapeutic agent when or when The therapeutic agent for the treatment of effective dose injects before completing when injection phase removes Wearable automatic injection device 600/700, Execution step 1020.

When injecting the therapeutic agent for the treatment of effective dose, stopper 615/715 and/or piston actuater 630/730 start receipts The administration of contracting mechanism terminates to shrink trigger.Stopper 615/715 and/or piston actuater 630/730 can include being connected to receipts The coupling member of contracting trigger.Coupling member can include tether, auricle or other link mechanism.Coupling member can have conjunction Suitable length so that when stopper 615/715 be moved into inject cartridge module 610/710 end when（So that injection doses Therapeutic agent）, coupling member triggering then start shrink trigger breech lock.

Once starting administration to terminate to shrink trigger, contracting mechanism just can make injection of therapeutic agent in shell 635/735 Cartridge module 610/710 stretches upwards and away from patient contacting portions, so that injection of therapeutic agent cartridge module 610/710 enters Inject state afterwards.In the exemplary embodiment, injection of therapeutic agent cartridge module 610/710 is from the shifting of injection state to rear injection state Movable property gives birth to audible sounds, such as " click " sound, and this provides the therapeutic agent audible indication that injection completes.Once shrinking, therapeutic agent is noted Shooting cylinder assembly 610/710 just projects into outside shell 635/735（As shown in figures 6 c and 7 c）, this provides Wearable automatic injection The state of device 600/700（For example, therapeutic agent injection completes）Visual instruction or device be in after inject state visual finger Show.

If however, removing Wearable device from patient body before the therapeutic agent injection for the treatment of effective dose completes 600/700, then skin sensor foot 660/760 extend to shell 635/735 outside and start removing in advance of contracting mechanism Shrink trigger.Once removing contraction trigger in advance to be activated, contracting mechanism just stretches upwards treatment in shell 635/735 Agent injection cartridge module 610/710 so as to away from patient contacting portions so that injection of therapeutic agent cartridge module 610/710 returns Punctured position.In the exemplary embodiment, removed from patient body before completing in the therapeutic agent injection for the treatment of effective dose During Wearable device 600/700, piston actuater 630/730 can connect towards injection in injection of therapeutic agent cylinder 610/720 Mouth 625/725 continues to move along.

In step 1025, when deflated, automatic grouting socket lock is engaged with grouting socket 625/725, to prevent from injecting Interface stretches again, thus providing acupuncture to protect.Grouting socket lock be once engage can be just to prevent grouting socket 625/725 Leave the component of shell 635/735, and grouting socket lock may be located in shell 635/735 near grouting socket 625/725 Place.Exemplary grouting socket lock can include but is not limited to plastic plate, metallic plate, clip etc..

Figure 11 A and 11B diagram includes the exemplary Wearable automatic injection device of syringe and exemplary connecting gear. The axonometric chart of Figure 11 A graphic display unit.Figure 11 B illustrates the exploded view of device feature.Automated injection device 1100 includes shell Part 1102, casing part 1102 include being arranged on patient contacting portion office, can be used for attaching a device to patient body or The adhesive layer 1104 of clothes.

Casing part 1102 in static or moveable mode, syringe 1106 is maintained in device 1100.Syringe 1106 preservation doses therapeutic agents and its far-end be connected to puncture syringe needle 1108.Piercing through syringe needle 1108 can be substantially along The longitudinal axis of syringe 1106 extend.In the pre-implant state of packaging, pierce through syringe needle 1108 and can be pierced needle cover 1105 Cover, before injection patient can remove puncture needle cover 1105 so that pierce through syringe needle 1108 injection state not by Cover.Pierce through needle cover 1105 to keep piercing through syringe needle and be formed by puncture syringe needle 1108 and be connected to puncture syringe needle 1108 Fluid conduit systems aseptic.In the exemplary embodiment, remove adhesive layer 1104 and can also remove puncture needle cover 1105.

Grouting socket button 1110 is arranged near puncture syringe needle 1108.Grouting socket button 1110 keeps being configured to Or by skin, therapeutic agent is injected on skin, in skin and any requires depth.Grouting socket 1112 can be configured to With respect to piercing through syringe needle 1108 generally an angle of 90 degrees, and can include providing pierce through syringe needle 1108 and grouting socket 1112 it Between fluid conduit systems connecting gear.In the exemplary embodiment, grouting socket 1112 can include single injection needle（By scheming Solid line in 11B illustrates）.In a further exemplary embodiment, grouting socket 1112 can include two or more injection needles （By the shown in phantom extra syringe needle in Figure 11 B）.In other exemplary embodiments of the invention, grouting socket 1112 can include executing The needleless liner being locally implanted of therapeutic agent and/or needleless paster.

In the pre-implant state of packaging, grouting socket 1112 can be injected into access flap 1113 and cover, in injection therapeutic agent Patient can remove grouting socket lid 1113 before.In injection state, grouting socket 1112 can be uncovered.In exemplary reality Apply in example, remove adhesive layer 1104 and can also remove grouting socket lid 1113.

Grouting socket button 1110 also includes preventing from piercing through the fluid conduit systems in syringe needle 1108 and grouting socket button 1110 Set up the partition 1111 being in fluid communication.Lid 1115 can be configured so that can be suffered from before injection in pre-implant state coverage The partition 1111 that person removes.In the exemplary embodiment, partition lid 1115 can be coupled and pierce through needle cover 1105, so that Remove another while removing one.

In the exemplary embodiment, in pre-implant state and rear injection state, pierce through needle cover 1105 and can cover puncture Syringe needle 1108, and grouting socket button 1110 is in vertically convex position because pierced needle cover 1105 is removed, thus Grouting socket 1112 is contracted in shell 1102.In this state, the partition 1111 of grouting socket button 1110 can position In the vertical top piercing through syringe needle 1108.Additionally, syringe 1106 can be in punctured position along the longitudinal axis of assembly 1106, Separate with the partition 1111 of grouting socket button 1110.

When removing puncture needle cover 1105 from puncture syringe needle 1108, grouting socket button 1110 drops to vertical lower portion Put, so that grouting socket 1112 projects into outside shell 1102 in injection phase.In the exemplary embodiment, by removing Pierce through needle cover 1105, grouting socket button 1110 can decline automatically.In a further exemplary embodiment, patient can be passed through Push down on grouting socket button 1110 to make grouting socket button 1110 decline.

In the exemplary embodiment, the decline of grouting socket button 1110 makes puncture syringe needle 1108 and grouting socket button 1110 partition 1111 aligns.The decline of grouting socket button 1110 also triggers makes syringe 1106 along its longitudinal axis towards note The actuated syringes device that the partition 1111 of incoming interface button 1110 advances.This make puncture syringe needle 1108 pierce through partition 1111 and with Grouting socket 1112 is set up and is in fluid communication.

Figure 12 A and 12B illustrative exemplary Wearable automatic injection device.The side view of Figure 12 A graphic display unit.Figure 12 B The axonometric chart of device feature is shown.Automated injection device 1200 is included with static with respect to shell 1202 or moveable side Formula keeps the shell 1202 of syringe 1204.Grouting socket button 1206 is arranged in shell 1202, near syringe 1204 And keep grouting socket（Do not draw）.Shell 1202 is included for being attached at injection phase or neighbouring adhesive layer 1208.

Reference picture 11A describes similar with the part in device 1200 other parts in device 1200 with 11B.

Figure 13 A-13C illustrative exemplary Wearable automatic injection device.The axonometric chart of Figure 13 A graphic display unit.Figure 13 B schemes The top view of showing device.The side view of the connecting gear of Figure 13 C graphic display unit.Automated injection device 1300 includes having for attached Be connected at injection phase or neighbouring adhesive layer 1303 shell 1302.Shell 1302 is with static with respect to shell 1302 or removable Dynamic mode keeps injection tube 1304.Injection tube 1304 is configured to preserve the therapeutic agent of doses.

Grouting socket button 1306 is arranged in shell 1302, near injection tube 1304.Grouting socket button 1306 can With keep or be connected to be configured on skin, in skin or by skin, therapeutic agent is injected into and any requires the one of depth Individual or multiple grouting sockets 1308.Grouting socket 1308 substantially can be prolonged with an angle of 90 degrees with respect to the longitudinal axis of injection tube 1304 Stretch, and pierce through syringe needle 1310 and can extend in an essentially parallel manner with the longitudinal axis of injection tube 1304.In the exemplary embodiment, Grouting socket 1308 can include single injection needle（Illustrated by the solid line in Figure 13 C）.In a further exemplary embodiment, note Incoming interface 1308 can include two or more injection needles（By the shown in phantom extra syringe needle in Figure 13 C）.Show in other In example property embodiment, grouting socket 1308 can include the needleless liner being locally implanted and/or needleless for executing therapeutic agent Paster.Grouting socket button 1306 can form or include connecting gear, and this connecting gear passes through to pierce through syringe needle 1310 in injection Set up between cylinder 1304 to grouting socket 1308 and be in fluid communication.

Grouting socket button 1306 can include when grouting socket button 1306 downward in the injection state injected The housing junction engaging with the casing part 1314 of shell 1302 during pressing divides 1312.Exemplary enforcement shown in Figure 13 C In example, housing junction divides the joint between 1312 and casing part 1314 to make the longitudinal direction of casing part 1314 and injection tube 1304 Diameter parallel ground moves towards the far-end of injection tube 1304, thus allows to pierce through the cylindrical portion of syringe needle 1310 and injection tube 1304 Set up and be in fluid communication.In a further exemplary embodiment, housing junction divides the joint between 1312 and casing part 1314 to make Injection tube 1304 is mobile towards piercing through syringe needle 1310 with the longitudinal axis parallel ground of injection tube 1304, thus allows to pierce through syringe needle 1310 are set up with the cylindrical portion of injection tube 2004 and are in fluid communication.In a further exemplary embodiment, housing junction divides 1312 Joint and casing part 1314 between makes injection tube 1304 and injection engagement buttons 1306 move towards each other, and thus allows thorn Thread a needle and 1310 set up with the cylindrical portion of injection tube 1304 and be in fluid communication.

Reference picture 11A describes similar with the part in device 1100 other parts in device 1300 with 11B.

Figure 14 A-14C diagram includes the exemplary Wearable automatic injection device of exemplary ejection cartridge module.Figure 14 A schemes The axonometric chart of showing device.The side sectional view of the injection tube that Figure 14 B diagram intercepts along longitudinal axis.Figure 14 C graphic display unit vertical Body top view.Automated injection device 1400 include having for be attached at injection phase or neighbouring adhesive layer 1403 shell 1402.Shell 1402 keeps injection tube 1404 in static with respect to shell 1402 or moveable mode.Injection tube 1404 is joined It is set to the therapeutic agent preserving doses.The near-end of injection tube 1404 includes stopper 1406, and the far-end bag of injection tube 1404 Include the partition 1408 of the therapeutic agent in collaborative sealing injection cylinder 1404.

Grouting socket button 1410 is arranged in shell 1402, near injection tube 1404.Grouting socket button 1410 exists Far-end keeps grouting socket, and this grouting socket is substantially extended with an angle of 90 degrees with respect to the longitudinal axis of injection tube 1404.Injection Interface button 1410 is connected to and will puncture through syringe needle 1412 and be maintained at the connecting gear 1411 near injection tube 1404.Pierce through syringe needle 1412 are extended in an essentially parallel manner with the longitudinal axis of injection tube 1404.Connecting gear 1411 includes fluid conduit systems, with by piercing through Fluid communication set up between injection tube 1404 and grouting socket by syringe needle 1412.In pre-implant state, pierce through syringe needle 1412 permissible It is partly extended in the far-end of injection tube 1404, but can separate with partition 1408.In injection state, stopper 1406 can To move in injection tube 1404, so that the Fluid pressure in injection tube 1404 makes partition 1408 towards puncture syringe needle 1412 Move forward.This makes puncture syringe needle 1412 pierce through partition 1408 and connect in injection tube 1404 and injection by piercing through syringe needle 1412 Set up between mouthful and be in fluid communication.

Reference picture 11A describes similar with the part in device 1100 other parts in device 1400 with 11B.

III. exemplary implantation system

Exemplary embodiment is provided for the difference exemplary injection system in the patient by the therapeutic agent injection of doses System and assembly.In some exemplary embodiments, the cylinder of the exemplary automated injection device containing therapeutic agent will can be connected to The grouting socket of shape part inserts or is applied to patient body, and therapeutic agent is injected in the patient.Implement in other examples In example, syringe needle can be will puncture through and be connected to the cylindrical portion comprising therapeutic agent, to derive therapeutic agent from cylindrical portion and permissible The grouting socket insertion piercing through syringe needle will be connected to or be applied to patient body, therapeutic agent is injected in the patient.

In some exemplary embodiments, as shown in figs, syringe can include cylindrical portion and be connected to cylinder The grouting socket of the far-end of shape part.Grouting socket can be coupled with patient body by for example inserting or being applied to patient, To inject the therapeutic agent being included in the cylindrical portion of syringe.Grouting socket can with respect to the longitudinal axis of cylindrical portion with Any proper angle alignment in the range of about 0 degree to about 180 degree, but not limited to this exemplary range.

Figure 15 diagram is suitable for the Exemplary syringe 1500 of exemplary automated injection device.Syringe 1500 include by It is configured to the cylindrical portion 1502 preserving doses therapeutic agent and extending between the proximal and distal ends along longitudinal axes L.Cylinder The far-end of shape part 1502 is connected to the one or more grouting sockets 1504 extending along longitudinal axes L.In exemplary embodiment In, grouting socket 1504 can include single injection needle（Illustrated by the solid line in Figure 15）.In a further exemplary embodiment, Grouting socket 1504 can include two or more injection needles（By the shown in phantom extra syringe needle in Figure 15）.Show in other In example property embodiment, grouting socket 1504 can include the needleless liner being locally implanted and/or needleless for executing therapeutic agent Paster.

Figure 16 diagram is suitable for the Exemplary syringe 1600 of exemplary automated injection device.Syringe 1600 include by It is configured to the cylindrical portion 1602 preserving doses therapeutic agent and extending between the proximal and distal ends along longitudinal axes L.Cylinder The far-end of shape part 1602 can include the elbow part 1604 generally 90 degree extending with longitudinal axes L.Elbow part 1604 far-end is connected to the grouting socket 1606 generally 90 degree extending with longitudinal axes L.Grouting socket 1606 can be by Be configured on skin, in skin or by skin, therapeutic agent is injected into and any requires depth.Those of ordinary skill in the art It should be understood that exemplary automated injection device can include extending or the longitudinal direction with respect to syringe along the longitudinal axes L of syringe Axis L becomes the grouting socket that any proper angle ground extends.Exemplary angle can include but is not limited to about 70 degree to about 110 Degree.In the exemplary embodiment, grouting socket 1606 can include single injection needle（Illustrated by the solid line in Figure 16）.Another In one exemplary embodiment, grouting socket 1606 can include two or more injection needles（By the volume shown in phantom in Figure 16 Outer syringe needle）.In other exemplary embodiments of the invention, grouting socket 1606 can be included for executing being locally implanted of therapeutic agent Needleless liner and/or needleless paster.

In some exemplary embodiments, as shown in FIG. 17 and 18, syringe can include cylindrical portion and be connected to cylinder The grouting socket of the far-end of shape part.Grouting socket can be coupled with patient body by for example inserting or being applied to patient, To inject the therapeutic agent being included in the cylindrical portion of syringe.Grouting socket can with respect to the longitudinal axis of cylindrical portion with Any proper angle alignment in the range of about 0 degree to about 180 degree, but not limited to this exemplary range.

In some exemplary embodiments, as shown in FIG. 17 and 18, syringe can include cylindrical portion and directly or Ground connection is connected to the grouting socket of the far-end of cylindrical portion.Pierce through syringe needle and can will be contained in controlling in the cylindrical portion of syringe Treat agent and be transported to grouting socket, and therapeutic agent can be injected in the patient by grouting socket.Can be by one or more Between part providing the connection pierced through between syringe needle and grouting socket.Exemplary connection parts can include, and for example, is arranged on cylinder Adapter between the far-end of shape part and grouting socket.

Figure 17 diagram is suitable for the Exemplary syringe 1700 of exemplary automated injection device.Syringe 1700 include by It is configured to proximally arrive remote extension along longitudinal axes L and be configured to preserve the cylindrical portion of doses therapeutic agent 1702.The far-end of cylindrical portion 1702 is connected to puncture syringe needle 1704.Pierce through syringe needle 1704 then by exemplary middle adaptation Device 1708 is connected to one or more grouting sockets 1706.Grouting socket 1706 can be configured on skin, in skin or By skin, therapeutic agent is injected into and any requires depth.More specifically, the proximal part of adapter 1708 is connected to puncture pin 1704, and the distal portions of adapter 1708 are connected to grouting socket 1706.Adapter 1708 can be in cylindrical portion Substantially 90 degree of alignment is set up between 1702 longitudinal axes L and grouting socket 1706.In the exemplary embodiment, grouting socket 1706 can include single injection needle（Illustrated by the solid line in Figure 17）.In a further exemplary embodiment, grouting socket 1706 can include two or more injection needles（By the shown in phantom extra syringe needle in Figure 17）.Implement in other examples In example, grouting socket 1706 can include the needleless liner being locally implanted and/or needleless paster for executing therapeutic agent.

Example adaptor 1708 is including first extending with being basically parallel to longitudinal axes L from cylindrical portion 1702 Divide the part of 1710 and the Part II 1712 extending with being basically perpendicular to longitudinal axes L from Part I 1710.More specifically, The near-end of Part I 1710 is connected to the far-end of cylindrical portion 1702.In the exemplary embodiment, Part I 1710 is near The far-end of Part II 1712 can be wrapped up in end.The far-end of Part I 1710 is connected to the near-end of Part II 1712.Second The far-end of part 1712 is connected to the near-end of grouting socket 1706.In the exemplary embodiment, may be integrally formed adapter 1708 Part I 1710 and Part II 1712.

Example adaptor can be formed by rigid material, including but not limited to plastic material, steel etc..Or, exemplary Adapter can be formed by elastomeric material, including but not limited to rubber etc..

The configuration being connected to the adapter 1708 of grouting socket 1706 allows grouting socket 1706 vertical with respect to syringe Extended to axis L with about 90 degree.Due to eliminating the demand of the grouting socket to bending, it is automatic that this configuration simplifies Wearable The manufacture of injection device.Exemplary grouting socket 1706 keeps low level to patient, can be properly inserted into simultaneously or be applied to trouble Person's body.Will be appreciated by those skilled in the art that exemplary grouting socket can be curved with respect to the longitudinal axis of syringe Song is to any proper angle being not limited to about 90 degree, for example, about 70 degree to about 110 degree.

In some exemplary embodiments, one or more fluids can be disposed piercing through to lead between syringe needle and grouting socket Pipe, to allow therapeutic agent to flow to syringe needle by piercing through syringe needle from cylindrical portion.Any suitable fluid conduit systems can be used Or fluid transport mechanism sets up one or more fluid conduit systems between puncture syringe needle and grouting socket.In exemplary embodiment In, the pierceable partition being in its intact state can stop puncture syringe needle and grouting socket from being in fluid communication.When puncture pin Head, when the injection state injected pierces through partition, can pierce through foundation between syringe needle and grouting socket by fluid conduit systems It is in fluid communication.

A part for Figure 18 illustrative exemplary automated injection device, wherein, the fluid conduit systems in connecting gear will puncture through pin Head and grouting socket are linked together.Described device includes injector assembly or injection cartridge module, injector assembly or injection tube Assembly has the cylindrical portion 1800 preserving doses therapeutic agent.The far-end of cylindrical portion 1800 is connected to puncture syringe needle 1802.Connecting gear 1804 is arranged to and pierces through syringe needle 1802 and contact or in its vicinity, and also and grouting socket（Do not paint Go out）Contact or in its vicinity.Connecting gear 1804 includes piercing through what foundation between syringe needle 1802 and grouting socket was in fluid communication Fluid conduit systems or path 1806.In a further exemplary embodiment, together with puncture syringe needle can be directly coupled to grouting socket, And there is not connecting gear between.

In the exemplary embodiment, the pre-implant state that connecting gear 1804 is included before injection makes puncture syringe needle 1802 Pierceable partition 1808 detached with the fluid conduit systems 1806 in connecting gear 1804.In the exemplary embodiment, note The injection state entering, syringe or injection tube can be mobile towards connecting gear 1804, so that pierce through syringe needle 1802 piercing through Partition 1808, to produce fluid even between cylindrical portion 1800, the fluid conduit systems 1806 of connecting gear 1804 and grouting socket Path.Thus, therapeutic agent can be flowed out to fluid conduit systems 1806 from cylindrical portion 1800 by piercing through syringe needle 1802.So Afterwards, therapeutic agent can be transferred in grouting socket by fluid conduit systems 1806, so that therapeutic agent is injected in the patient.

Figure 19 illustrates for piercing through syringe needle（Do not draw）And grouting socket（Do not draw）Between provide fluid conduit systems 1902 Exemplary connecting gear 1900.Fluid conduit systems 1902 can include：The groove 1904 extending at center, therapeutic agent passes through groove 1904 flow to grouting socket from puncture syringe needle；And convex wall part 1906, it extends along the edge of groove 1904 so that will Confines fluid is in groove 1904.Fluid conduit systems 1902 can take any suitable form and size.In illustrative embodiment In, fluid conduit systems 1902 have with the second generally flat part 1910 with the generally flat part 1908 of about 90 degree of first aliging.

Fluid conduit systems 1902 can be included for making therapeutic agent from the fluid intake 1912 piercing through syringe needle entrance and be used for making Therapeutic agent exits into the fluid issuing 1914 of grouting socket.Fluid intake 1912 can be coupled, directly or indirectly, to pierce through pin The far-end of head.In the exemplary embodiment, can be by pierceable partition（Do not draw）Be arranged at fluid intake 1912, with every When piece is intact, prevention fluid flows into from puncture syringe needle, and allows fluid when partition is pierced needle pierces from puncture pin Head flows into.Fluid issuing 1914 can be coupled, directly or indirectly, to the near-end of grouting socket, so that in fluid conduit systems 1902 and note Fluid flow path is set up between incoming interface.

Or, 1912 can serve as fluid issuing, and 1914 can serve as fluid intake.In this exemplary embodiment In, fluid intake 1914 can be coupled, directly or indirectly, to pierce through syringe needle, and fluid issuing 1912 can directly or indirectly join It is connected to grouting socket.

Connecting gear 1900 can be formed by two casing parts 1916 and 1918 stacked together.In exemplary enforcement In example, fluid conduit systems 1902 can be formed on the surface of part 1916, and part 1918 can be layered in fluid conduit systems On 1902, thus sealing the edge of fluid conduit systems 1902, to prevent fluid from revealing from fluid conduit systems.One or many can be passed through Individual mechanical interlocking mechanism, for example, one or more securing members, snap-fastener, chemical gluing, ultrasonic bonding etc., compress two shells Part 1916 and 1918.

Using any suitable technology, fluid conduit systems 1902 can be formed on the surface of casing part 1916.Exemplary In embodiment, the convex wall part 1906 of fluid conduit systems 1902 can be formed by the low-durometer material being molded as liner, to seal The flow path of therapeutic agent.In a further exemplary embodiment, it is possible to use laser welding follows the trail of the circumference around groove 1904 Path to produce the sealing around groove 1904 and to be combined together two casing parts 1916 and 1918 simultaneously.

In a further exemplary embodiment, together with puncture syringe needle can be directly coupled to grouting socket, and there is not Jie In middle connecting gear.

Figure 20 illustrates in the syringe with the puncture syringe needle 2004 being connected to cylindrical portion 2006 and grouting socket （Do not draw）Between provide fluid conduit systems 2002 exemplary connecting gear 2000.Connecting gear 2000 can be included with partition 2010 Part I 2008, partition 2010 is arranged near puncture syringe needle 2004.

The Part I 2008 of connecting gear 2000 can include the inner hollow space for accommodating therapeutic agent and connection Inlet port 2012 to one end of hollow pipe 2014.The other end of hollow pipe 2014 is direct or indirect（For example, by with first Divide 2008 similar Part II）It is connected to grouting socket.Hollow pipe 2014 is provided from puncture syringe needle 2004 to grouting socket Fluid path.Hollow pipe 2014 can take any suitable form, linear and size.In an illustrative embodiment, hollow pipe 2014 are extended with the longitudinal axis substantiated right angles of cylindrical portion 2006 ground.

In the exemplary embodiment, connecting gear 2000 can move up and/or down along vertical axis.Here is implemented In example, pre-implant state before injection（For example, when puncture syringe needle is covered by needle cover）, connecting gear 2000 can locate In the vertically convex position piercing through syringe needle 2004 top so that pierce through syringe needle 2004 not with connecting gear 2000 in partition 2010 alignment, thus prevent from piercing through being in fluid communication between syringe needle 2004 and connecting gear 2000.When starting injection（For example, when When puncture syringe needle 2004 removes syringe lid）, connecting gear 2000 can be automatically lowered vertical lower position, so that Piercing through syringe needle 2004 becomes to align with the partition 2010 in connecting gear 2000, thus allows to pierce through syringe needle 2004 puncture partition 2010.Exemplary embodiment can provide perpendicular for making connecting gear 2000 drop to from vertically convex position when starting injection Any suitable actuating mechanism of straight lower position.

In the exemplary embodiment, pierce through syringe needle 2004 to be initially connected to or be arranged to against Part I 2008.In another embodiment, syringe may be at the punctured position in Wearable automatic injection device, and pierces through pin 2004 initially can be separated with the Part I 2008 of connecting gear 2000.In this embodiment, pre- note before injection Enter state, piercing through syringe needle 2004 can be separated with the partition 2010 in Part I 2008, and can not be with connecting gear 2000 fluid communication.When starting injection, syringe can be moved forward in device by injection tube or actuated syringes device Extended position, and pierce through syringe needle 2004 and can pierce through partition 2010, so that therapeutic agent flows to from cylindrical portion 2006 Connecting gear 2000.Exemplary embodiment can provide any suitable syringe or injection tube actuating mechanism, is used for making tubular Part and/or injection cartridge module advance, thus piercing through partition and passing through between shell inherence punctured position and extended position Therapeutic agent is transferred to patient body by grouting socket.

The advantage of exemplary connecting gear 2000 is, pierces through syringe needle 2004 and the motion of grouting socket is uncorrelated and mutual Mutually independent.For example, will puncture through syringe needle 2004 and be connected to the mechanism of inlet port 2012 needs to consider how this connection can affect to couple Outlet to the connecting gear 2000 of grouting socket.

Figure 21 illustrates in the syringe with the puncture syringe needle 2104 being connected to cylindrical portion 2106 and grouting socket （Do not draw）Between provide fluid conduit systems exemplary connecting gear 2100.Connecting gear 2100 can include being connected to puncture The intake section of syringe needle 2104（Do not draw）With the exit portion that can be connected to grouting socket（Do not draw）.Hollow pipe 2108, example As jumper pipe, can be used for the intake section of connecting gear is connected to the exit portion of connecting gear.Hollow pipe 2108 provides Fluid path from puncture syringe needle 2104 to grouting socket.Hollow pipe 2108 can take any suitable form, linear and big Little.In an illustrative embodiment, hollow pipe 2108 and the longitudinal axis of cylindrical portion 2106 extend at a substantially right angle.

In the exemplary embodiment, can to include being arranged on puncture syringe needle 2104 attached for the intake section of connecting gear 2100 Near partition（Do not draw）.Can be between cylindrical portion 2106 and connecting gear 2100 using piercing through syringe needle 2104 puncture partition Set up and be in fluid communication.In the exemplary embodiment, the exit portion of connecting gear 2100 can include being arranged on grouting socket Neighbouring partition（Do not draw）.Pierce through partition using grouting socket and can set up stream between connecting gear 2100 and patient body Body connects.

In the exemplary embodiment, connecting gear 2100 can move up and/or down along vertical axis.Here is implemented In example, pre-implant state before injection（For example, when puncture syringe needle is covered by needle cover）, connecting gear 2100 can locate In the vertically convex position piercing through syringe needle 2104 top so that pierce through syringe needle 2104 not with connecting gear 2100 in partition Alignment, thus prevents from piercing through being in fluid communication between syringe needle 2104 and connecting gear 2100.When starting injection（For example, when from thorn Thread a needle 2104 when removing syringe lid）, connecting gear 2100 can be automatically lowered vertical lower position, so that piercing through Syringe needle 2104 becomes to align with the partition in connecting gear 2100, thus allows to pierce through syringe needle 2104 puncture partition.Exemplary reality Applying example can be provided for making connecting gear 2100 drop to vertical lower position from vertically convex position when starting injection Any suitable actuating mechanism.

In the exemplary embodiment, pierce through syringe needle 2104 to be initially connected to or be arranged to against Part I 2108.In another embodiment, syringe may be at the punctured position in Wearable automatic injection device, and pierces through pin 2104 initially can be separated with connecting gear 2100.In this embodiment, pre-implant state before injection, pierces through syringe needle 2104 can be separated with partition, and can not be in fluid communication with connecting gear 2100.When starting injection, syringe can lead to Cross the extended position that injection tube or actuated syringes device move forward in device, and pierce through syringe needle 2104 can pierce through every Piece, so that therapeutic agent flows to connecting gear 2100 from cylindrical portion 2106.Exemplary embodiment can provide any suitable Syringe or injection tube actuating mechanism, be used for making cylindrical portion and/or injection cartridge module in shell inherence punctured position and to stretch Advance between putting in exhibition position, thus piercing through partition and by grouting socket, therapeutic agent being transferred to patient body.

In a further exemplary embodiment, together with puncture syringe needle can be directly coupled to grouting socket, and there is not Jie Enter the connecting gear of centre.

In exemplary embodiment shown in Figure 17-21, sealing and reliable fluid path by therapeutic agent from syringe or Soleno- groove that the cylindrical portion of injection tube is transmitted through in pierced partition and connecting gear simultaneously eventually enters into grouting socket. This configuration allows to pierce through needle assembly and grouting socket assembly moves independently of each other, and this contributes to grouting socket and is carrying out Rear injection state after injection is retracted in shell, makes puncture syringe needle be in the position piercing through partition simultaneously.

Figure 22 diagram may be used to the syringe 2202 or injection cartridge module shell in Wearable automatic injection device Interior Exemplary syringe or the injection tube actuator 2200 proceeding to extended position towards grouting socket from punctured position.Syringe The near-end of assembly or injection cartridge module can be connected to biasing member 2204, for example, driving spring, it is to injector assembly or note Shooting cylinder assembly applying power is with towards connecting gear（Do not draw）In the mobile injector assembly of partition or injection cartridge module.Syringe Or injection tube actuator 2200 can resist the bias force of biasing member, and can be by cylindrical portion in the way of reliable and stable And/or injection cartridge module keeps and is locked in punctured position.In the exemplary embodiment of setting syringe, syringe can join It is connected to the puncture syringe needle piercing through partition.In the another exemplary embodiment of setting injection tube, connecting gear can arrange spinosity Wear the puncture syringe needle of partition.

When being triggered by suitable trigger mechanism in the state of injection, syringe and injection tube actuator 2200 are so that note Emitter assemblies or injection cartridge module move forward towards partition in the presence of the power of biasing member.In the exemplary embodiment, Syringe and injection tube actuator 2200 can be configured and/or be set to certain distance, makes injector assembly or note to control Trigger force size needed for punctured position proceeds to extended position for the shooting cylinder assembly.

Any suitable trigger mechanism may be used to trigger syringe or injection tube actuating system.In exemplary embodiment In, when Wearable automatic injection device from pre-implant state change to injection state when, trigger mechanism can trigger note automatically Emitter or injection tube actuating system.In the exemplary embodiment, grouting socket button moves in inside the shell straight down with note Fluid path is provided, this can provide touching of triggering plunger actuation system between emitter assemblies or injection cartridge module and grouting socket Have an effect.In a further exemplary embodiment, injector assembly or injection cartridge module move forward with syringe group in shell Fluid path is set up, this can provide triggering syringe or inject touching of cartridge system between part or injection cartridge module and grouting socket Have an effect.In a further exemplary embodiment, patient can manually trigger syringe or injection cartridge system.

Pre-implant state before injection, is arranged on the puncture needle cover of the far-end of syringe 2202, for example rigidly Needle cover（Do not draw）, can protectively cover puncture syringe needle.Pierce through needle cover can keep piercing through syringe needle and by puncture pin The fluid conduit systems that head is formed and coupled to pierce through syringe needle are aseptic.In this stage, it is covered with needle cover due to piercing through syringe needle, therefore The far-end of syringe 2202 has the first larger diameter.So, the grouting socket button including partition keeps being in puncture syringe needle The vertically convex position of the side of covering, and partition not with pierce through syringe needle align.Pierce through needle cover when removing from syringe with remarks Fashionable（For example, manually removed by patient or removed by automechanism）, grouting socket button is not due to rigidly being pierced Skull of threading a needle is removed and can be descended to vertical lower position, and the partition in grouting socket button aligns with piercing through syringe needle. Therefore, remove puncture needle cover so that grouting socket button vertically drops to its vertical lower position in convex position from it.Injection The decline of interface button applies trigger force to syringe or injection tube actuator 2200 then, and as syringe or injection tube The trigger mechanism of actuator 2200.

Figure 23 diagram includes Part I 2302, Part II 2304 and the hinge being arranged between the first and second parts The Exemplary syringe of part 2306 or injection tube actuator 2300.Hinge fraction 2306 allows the first and second parts around hinge Chain relative to each other rotates.In different rotations configures, the first and second parts can have each other in about 0 degree of peace treaty Exemplary angle between 180 degree.Actuator 2300 can be connected to syringe and/or grouting socket button.When partition and/or Grouting socket button be in vertically convex position when, actuator 2300 can make syringe be held in place at its punctured position.When When partition and/or grouting socket button are in vertical lower position, actuator 2300 can discharge syringe, so that biasing Syringe can be pushed forward to its extended position by component, to pierce through partition.

IV. example piston actuating system and grouting socket pinch system

Exemplary embodiment provide for activate Wearable automatic injection device cylindrical portion in stopper so that Obtain stopper to move forward in cylindrical portion and discharge the plunger actuation of the doses therapeutic agent being included in cylindrical portion System.Any suitable trigger mechanism may be used to trigger plunger actuation system.In the exemplary embodiment, work as Wearable When pre-implant state change is to injection state, trigger mechanism can trigger plunger actuation system to automated injection device automatically.? In exemplary embodiment, grouting socket button moves in inside the shell straight down with injector assembly or injection cartridge module and note Fluid path is provided, this can provide the trigger force of triggering plunger actuation system between incoming interface.In another exemplary embodiment In, injector assembly or injection cartridge module move forward with injector assembly or injection cartridge module and grouting socket in shell Between set up fluid path, this can provide triggering plunger actuation system trigger force.In a further exemplary embodiment, patient Plunger actuation system can manually be triggered.

Some exemplary embodiments provide the plunger actuation system making syringe piston activate with rapid rate, so that with quick Therapeutic agent is injected in the patient by rate.Exemplary Rapid Implementation example can inject about 0.1 milli in about one second to about 30 seconds Rise to the therapeutic agent of about 1 milliliter of amount, but exemplary charge velocity not limited to this exemplary range.In some exemplary embodiments In, the therapeutic agent of about 0.1 milliliter to about 1 milliliter amount can be injected in the range of the time period of about 3 seconds to about 5 seconds.Show at some In example property embodiment, the treatment of about 0.1 milliliter to about 1 milliliter amount can be injected in about 20 seconds or the time period being shorter than 20 seconds Agent.Exemplary embodiment can provide the linear injection curve of therapeutic agent, so that charge velocity substantially constant in time.? In some situations, linear injection curve can mitigate the sense of discomfort of patient.

Figure 24 diagram, using the exemplary automated injection device 2400 of the piston actuated mechanism based on fluid, wherein, uses The movement of the Fluid pressure of working fluid and/or working fluid moving plug in the cylindrical portion of syringe or injection tube.Live Plug actuating mechanism includes providing one or more fluid circuits of the power of working fluid to stopper, so that from syringe or injection tube Cylindrical portion 2404 extrude doses therapeutic agent.Wearable automatic injection device 2400 can include pressure elements 2406, it stores or is connected to the incompressible workflow body source providing Fluid pressure.Exemplary operation fluid can include But it is not limited to water, air, oil etc..Exemplary compression element can include but is not limited to resilient bladder, master cylinder, spring add Load formula syringe etc..

Pressure elements 2406 can be connected to flow restrictor 2408 via pipe.Flow restrictor 2408 can limit work Make the flow of fluid, so that the Fluid pressure of flow restrictor upstream is more than the Fluid pressure in flow restrictor downstream.Stream Body limiter 2408 can include aperture in about 0.001 inch to about 0.01 inch range for the diameter, but exemplary flow rate The diameter not limited to this exemplary range in controller aperture.The aperture of fluid restrictor 2408 can have in about 10mm to about Length in the range of 50mm, but the length not limited to this exemplary range in exemplary flow controller aperture.

Exemplary embodiment can configure the many features of injected system, to control total injection length of therapeutic agent.Example Property embodiment be also based on the viscosity of working fluid and/or therapeutic agent and configure the many features of injected system.Example feature The diameter in aperture, the length in aperture, viscosity of working fluid etc. can be included but is not limited to.For example, it is possible to reduction flow restriction The diameter in the aperture of device is to increase total injection length.

Flow restrictor 2408 can be connected to stopper via pipe 2412.When first from pressure via flow restrictor 2408 During part 2406 release working fluid, the Fluid pressure of working fluid drives forwards stopper in cylindrical portion 2404, so that from cylinder The therapeutic agent of shape part 2404 discharging doses.

In the exemplary embodiment, pre-implant state before injection, working fluid will not be from pressure elements 2406 quilt Release.In the exemplary embodiment, inject trigger（Do not draw）Pressure elements 2406 can be connected to, so that work as opening During dynamic injection trigger, working fluid is released to the pipe that pressure elements is connected to stopper from pressure elements 4106.With Afterwards, the Fluid pressure of working fluid makes stopper advance in cylindrical portion 2404, thus injects in the patient therapeutic agent.From And, from the flowing of working fluid, the fluid circuit set up and flow restrictor provide adjusted power to stopper.

In the exemplary embodiment, with linear injection curve, that is, with substantially invariable charge velocity, inject therapeutic agent.Logical The high pressure of working fluid that the pressure elements 2406 of inflow-rate of water turbine limiter 2408 upstream provides and flow restrictor 2408 provide Damping action realize linear injection curve.The pressure of flow restrictor 2408 upstream can be tieed up with respect to the stick-slip power presenting Hold in high level, thus realizing altitude-damp system.In order that stopper moves forward in cylindrical portion 2404, it is right that stopper needs Working fluid evacuation between flow restrictor 2408 and cylindrical portion 2404, the suitable degree of this difficult to reach, because stream Body can not compress substantially.

Exemplary dampened hydraulic pressure infusion circuit is via adjusting volume flow rather than by directly applying force to so that stopper Mobile, thus minimize therapeutic agent and inject the stick-slip phenomenon in curve.

Figure 25 illustrates when the exemplary implantation system injection by Figure 24 in time（Second）The therapeutic agent accumulation body of change Long-pending（Milliliter）Chart, this exemplary implantation system includes having showing of about 0.008 inch of exemplary diameter and about 34.3mm First exemplary flow rate limiter of example property length.Total injection length for injecting about 1 milliliter of therapeutic agent is about 20 seconds.Saying In bright property chart, injection curve is substantially linear, i.e. substantially constant in time, and does not show heavy dose or the table of beginning Show the inconsistent suddenly change of charge velocity or flex point.

Figure 26 is the example to provide the power extruding therapeutic agent from injection cartridge module using one or more fluid circuits The schematic diagram of property automated injection device 2600.Figure 27 is the top view of exemplary means 2600.Exemplary automated injection device The cylindrical portion 2602 of 2600 therapeutic agents including comprising doses.The far-end of cylindrical portion 2602 is disposed proximate to or joins It is connected to the puncture syringe needle that pierced needle cover 2604 protectively covers（Pierced needle cover 2604 is hidden）.Pierce through needle cover 2604 can keep pierce through syringe needle and by pierce through syringe needle is formed be connected in parallel to puncture syringe needle fluid conduit systems aseptic.Device 2600 wraps Include with partition and support grouting socket（Do not draw）Grouting socket button.In the exemplary embodiment, device 2600 can To include the grouting socket support 2606 for keeping grouting socket.In a further exemplary embodiment, piercing through syringe needle can be It is directly coupled to grouting socket not used in the case of the intermediate support part of grouting socket.In the exemplary embodiment, such as Shown in figure, grouting socket substantially orthogonally can be extended with the plane of device, and can pass through grouting socket support 2606 quilt It is held in place.Grouting socket lock 2608 can be configured so that and just prevents the grouting socket being in punctured position from projecting into once joint Outer side and may be located in shell at the grouting socket.

In the exemplary embodiment, syringe or injection tube actuator 2610 can be configured so that and so that cylindrical portion 2602 is existed Inside the shell is advanced towards partition.Trigger can be configured so that for example when pressing down on grouting socket button or works as and removes puncture Triggering syringe or injection tube actuator 2610 during needle cover 2604.

In the exemplary embodiment, the master cylinder 2612 comprising working fluid is positioned to provide Fluid pressure with tubular Actuated plug 2614 in part 2602.Master cylinder 2612 can be connected to injection trigger 2616, and injection trigger 2616 is being opened When dynamic, release working fluid makes itself and stopper 2614 be in fluid communication and allow Fluid pressure to make stopper 2614 in cylindrical portion Advance in 2602.

Exemplary embodiment also provides for will be vertical outside grouting socket crust of the device in patient contacting area Lower position（Or stretch or expanded position）It is retracted to the vertically convex position in crust of the device（Or punctured position）Injection connect Mouth pinch system.Wearable automatic injection device 2600 includes making grouting socket button from the injection state injected The stretching, extension of inside the shell or expanded position are increased to the punctured position of the inside the shell in the rear injection state after injection automatically.Showing In example property embodiment, contracting mechanism can be telescopic element.Master cylinder 2612 can be connected to contraction trigger, shrinks triggering Device discharges working fluid when being activated to be made itself and contracting mechanism be in fluid communication and allows Fluid pressure to start contracting mechanism.

The top view of Figure 28 graphic display unit 2600, shows the conduit that master cylinder 2612 is connected to flow restrictor 2804 2802, flow restrictor 2804 is connected to the conduit 2806 of the stopper in the cylindrical portion 2602 of device and via valve 2812 （Such as check-valves）Master cylinder 2612 is connected to the conduit 2808 of contracting mechanism 2810.The schematic diagram of Figure 28 graphic display unit 2600.

Check-valves 2812 can have suitable Opening pressure, under this Opening pressure or when being more than this Opening pressure, only Returning valve 2812 allows fluid to flow into the conduit 2808 being connected to contracting mechanism 2810.In the exemplary embodiment, Opening pressure is high The maximum fluid pressure in conduit 2806 needed in the injection state-driven stopper being injected.Otherwise it is undesirable to ground, note Before incoming interface contraction process may begin at injection period or even injection.In the exemplary embodiment, in the note being injected Enter in state, when the mobile end of stopper, the pressure in conduit 2806 is more than Opening pressure.Otherwise, when the mobile knot of stopper Shu Shi, the pressure in conduit 2808 can be not enough to start contracting mechanism 2810.In master cylinder 2612, the amount of working fluid be enough to inject Whole dose of therapeutic agent simultaneously starts contracting mechanism 2810.

In the exemplary embodiment, contracting mechanism 2810 and check-valves 2812 can be configured so that detached.Show another In example property embodiment, contracting mechanism 2810 and check-valves 2812 can be configured so that discrete component, for example, be arranged to reversely every Film（inverting diaphragm）.

Figure 30 diagram pressure after check-valves and after stopper in the exemplary embodiment（psi）In time（Second）Become The chart changed.In the exemplary embodiment, the Opening pressure of check-valves can be about 7.5 psi, and flow restrictor aperture Diameter can be about 0.008 inch.

In the injection state injected, flow restrictor 2804 can make the pressure in conduit 2802 reach about 10 to about 15 psi, simultaneously the pressure in conduit 2806 can reach about 5 to about 6 psi.Thus, when stopper is mobile in injection period, Check-valves 2812 prevent any working fluid from entering conduit 2808.Once stopper stops moving at the end of injection, i.e. when When cylindrical portion 2602 discharges therapeutic agent, the pressure in conduit 2806 increases to above 7.5 psi.This makes 2812 dozens, check-valves Open it is allowed to working fluid inflow catheter 2808, thus start contracting mechanism 2810.Contracting mechanism 2810 unlocks grouting socket then Lock and shrink the grouting socket button/support 2606 of supporting grouting socket.Due to being equalized based on the pressure in hydraulic circuit, because This grouting socket contraction process guarantee grouting socket shrink before inject whole dose of therapeutic agent, maximize therapeutic agent utilization and Minimize required excess filling in cylindrical portion 2602.

Any suitable trigger mechanism may be used to trigger grouting socket pinch system.In the exemplary embodiment, when When injecting state change to rear injection state, trigger mechanism can trigger grouting socket to Wearable automatic injection device automatically Pinch system.In the exemplary embodiment, injection complete treatment effective dose therapeutic agent can trigger grouting socket shrink system System.In a further exemplary embodiment, remove device from patient before the therapeutic agent completing treatment effective dose in injection permissible Triggering grouting socket pinch system.In a further exemplary embodiment, patient can trigger grouting socket pinch system manually.

The side view of Figure 31 illustrative exemplary automated injection device 3100, wherein, Wearable automatic injection device 3100 Shell 3102 include skin sensor foot 3104, in the exemplary embodiment, skin sensor foot 3104 is to be housed in shell 3102 close injection phase partly lower or in structure.In the exemplary embodiment, injection therapeutic agent before and injection Period, skin sensor foot 3104 is maintained in a part for the downside of shell 3102 or forms this part.When Wearable from When dynamic injection device 3100 is attached to injection phase and is activated, skin sensor foot 3104 can move freely, but Constrained by injection phase.In the exemplary embodiment, when removing Wearable automatic injection device 3100 from injection phase, no Complete by whether therapeutic agent injects, skin sensor foot 3104 is no longer constrained, and extend and project into the side of shell 3102 Outside edge.This starts contraction trigger then.When contraction trigger is activated, contracting mechanism shrinks grouting socket, and this also may be used So that grouting socket button is increased to vertically convex position from vertical lower position, so that grouting socket button is from shell 3102 top boss and grouting socket is contracted in shell 3102.

V. exemplary grouting socket protection system

Exemplary embodiment provides different exemplary grouting socket protection systems, to make grouting socket in injection treatment Rear injection state holding after pre-implant state before agent and injection is in the contraction in Wearable automatic injection device Position.Grouting socket is shunk and protection can prevent unexpected needle stick injury patient or Wearable automatic in crust of the device Any other people near injection device.

Figure 32 A and 32B diagram keeps grouting socket 3202 to be in the punctured position in the shell 3204 of automated injection device Exemplary grouting socket protection system 3200.Exemplary grouting socket can include single injection needle, multiple injection needle, Needleless liner, needleless paster etc..

In the exemplary embodiment, grouting socket 3202 can move away from or towards patient body with respect to shell 3204 Dynamic.When being in shell 3204 position further away from patient body when grouting socket 3202, grouting socket 3202 is in punctured bit Put and not projecting to outside shell 3204.When device is in pre-implant or rear injection state, grouting socket 3202 is in receipts Condense and put.When grouting socket 3202 is in the position being closer to patient body in shell 3204, grouting socket 3202 is in be stretched Exhibition or expanded position and from shell 3204 completely or partially projection.Shell 3204 can arrange jagged 3206, injection Interface 3202 can be projected into outside shell 3204 by breach 3206.When device is in injection state, grouting socket 3202 It is in stretching, extension or expanded position.

Grouting socket protection system 3200 adopts barrier mechanism 3208, when grouting socket 3202 is in punctured position, screen Barrier mechanism 3208 prevents the rear injection state after grouting socket 3202 pre-implant state before injection and injection from shell 3204 projections.Figure 32 A illustrates system 3200, and wherein, grouting socket 3202 is in stretching, extension or expanded position and passes through breach 3206 completely or partially project into outside shell 3204, such as in the injection state injected.In this case, barrier Mechanism 3208 is removed from breach 3206, so that breach 3206 opens and grouting socket 3202 to the outside of shell 3204 The outside of shell 3204 can be projected into by breach 3206.Figure 32 B illustrates system 3200, and wherein, grouting socket 3202 is in Punctured position and not from shell 3204 projection, such as in pre-implant state and rear injection state.In this case, barrier mechanism 3208 are alignd with breach 3206 and cover breach 3206 so that breach 3206 no longer open to the outside of shell 3204 and Grouting socket 3202 can not project into the outside of shell 3204 by breach 3206.In the exemplary embodiment, barrier mechanism 3208 can be in the primary importance exposing breach 3206（In Figure 32 A）With the second position covering breach 3206（In Figure 32 B In）Between be rotatably moved around the point of rotation.

Another exemplary grouting socket that Figure 33 A and 33B diagram is arranged in the shell 3302 of automated injection device is protected Protecting system 3300.Shell 3302 can arrange jagged, and grouting socket can be projected into outside shell 3302 by breach.Example Property grouting socket can include but is not limited to an injection needle, multiple injection needle, needleless paster or pump etc..In exemplary reality Apply in example, automated injection device include can with respect to shell 3302 along vertical axis V away from or towards patient body movement Grouting socket.Exemplary grouting socket can include single injection needle, multiple injection needle, needleless liner, needleless paster etc.. When device is in pre-implant or rear injection state, grouting socket is in further away from the punctured position of patient body and not projecting To outside shell 3302.When device is in injection state, grouting socket is in the stretching, extension being closer to patient body or launches position Put and completely or partially project into outside shell 3302.In the exemplary embodiment, grouting socket can directly or Ground connection is connected to auricle or pin 3308.Auricle 3308 is the mechanical component being connected to grouting socket, so that grouting socket is in device It is in and extends during injection phase, and be located at punctured position when device is in pre-implant or rear injection state.

Grouting socket protection system 3300 includes locking bushing 3306, and it is arranged near grouting socket, for pre- Grouting socket is locked in punctured position by injection state and rear injection state.Exemplary locking bushing 3306 is generic tubular or circle Cylindrical component, it can rotate around the center line rotation axiss extending through this component.It is narrow that locking bushing 3006 can include L-shaped Groove or groove, it includes Part I 3304 and the Part II perpendicular to vertical axis V extension extending along vertical axis V 3310.Auricle 3308 is arranged to be contained in slit and extend to outside locking bushing 3306 through slit.

Grouting socket protection system 3300 is additionally included in the skin being coupled with locking bushing 3306 at wedge interface 3314 and passes Sensor foot 3312.When removing Wearable automatic injection device 3300 from injection phase, skin sensor foot can be started 3312.Upon being activated, skin sensor foot 3312 can move with respect to interface 3314 to project into outside shell 3302.Skin Skin sensor foot 3312 makes locking bushing 3306 around its center rotation axiss rotation with respect to the movement at interface 3314.Starting Before skin sensor foot 3312, auricle 3308 may be located at the connecting portion between the first and second parts of slit（In Figure 33 A Middle diagram）.In this position, auricle 3308 can be along the Part I 3304 of slit（Extend along vertical axis V）Slide downward.This Then grouting socket is allow to move to extended position from punctured position together with auricle 3308, can in this position grouting socket For therapeutic agent is injected in the patient.When the startup of skin sensor foot 3312 makes locking bushing 3306 rotate, slit Part II 3310 flatly move so that auricle 3308 be located at slit Part II 3310 end（In figure Illustrate in 33B）.In this position, auricle 3308 no longer can be along vertical axis V slide downward.This then stop grouting socket and Auricle 3308 moves to extended position from punctured position together, and grouting socket is effectively locked at the receipts in shell 3302 Condense and put.

Figure 34 diagram holding grouting socket is injected into interface cradle 3404 and is maintained in the shell 3404 of automated injection device Punctured position exemplary grouting socket protection system 3400.In the exemplary embodiment, grouting socket can be with respect to outer Shell 3404 moves along vertical axis V away from or towards patient body.When grouting socket is in shell 3404 further away from patient's body During the position of body, grouting socket may be at punctured position and can not projecting to outside shell 3404.In exemplary enforcement In example, when device is in pre-implant or rear injection state, grouting socket is in punctured position.When grouting socket is in shell Be closer in 3404 patient body position when, grouting socket may be at stretching or expanded position and can be from shell 3404 Completely or partially projection.Shell 3404 can arrange jagged, and grouting socket can project into shell 3404 by breach Outside.In the exemplary embodiment, when device is in injection state, grouting socket is in stretching, extension or expanded position.

Grouting socket protection system 3400 can include the grouting socket lock 3408 being connected to grouting socket support 3402.? In exemplary embodiment, grouting socket lock 3408 can be the pivot or rotation structure that can pivot around pivotal point or interface or rotate Part.Grouting socket lock relieving mechanism 3410 can be configured so that locks 3408 near to or in contact with grouting socket.Grouting socket protection system System 3400 can also be included by skin sensor foot（Not shown）The biasing mechanism 3412 of biasing.

When device is located at injection phase, skin sensor foot is not activated and grouting socket is locked at relieving mechanism 3410 In off-position.This stops the locking that grouting socket is locked between relieving mechanism 3410 and grouting socket lock 3408 from interacting, and permits Permitted grouting socket support 3402 and be moved down into extended position along vertical axis V from punctured position, to project into outside shell 3404 Side.When by removing device and starting skin sensor foot from injection phase, biasing mechanism 3412 triggering grouting socket lock is released Laying mechanism 3410 makes it along straight line or moves in a rotative pattern, so that grouting socket lock relieving mechanism 3410 and grouting socket Lock 3408 interacts and locks grouting socket lock 3408.In this position of locking grouting socket lock 3408, grouting socket support 3402 are locked in convex position, and wherein, grouting socket is contracted in shell 3404.

In the exemplary embodiment, pierce through syringe needle and can be directly coupled to grouting socket, and do not exist for grouting socket Intermediate support part.In a further exemplary embodiment, piercing through syringe needle can be by the intermediate support portion for grouting socket Part is connected to grouting socket.

Figure 35 A-35E diagram keeps grouting socket to be injected into the shell that interface cradle 3502 is maintained at automated injection device The exemplary grouting socket protection system 3500 of the punctured position in 3504.Figure 35 A illustrates the axonometric chart of system 3500；Figure 35 B The top view of diagram system 3500；Figure 35 C illustrates the first side view of system 3500；Figure 35 D illustrates the second side of system 3500 View, wherein, described device is in injection state；And Figure 35 E illustrates the second side view of system 3500, wherein, described dress Put and be in pre-implant or rear injection state.

Device can include shell 3504 and be arranged on the injection being used for keeping aliging along vertical axis V in shell 3504 The grouting socket support 3502 of interface.Shell 3504 can be included for allowing grouting socket to project into shell 3504 outside and incite somebody to action Therapeutic agent injection breach in the patient.The vertical shift of grouting socket support 3502 allows grouting socket in grouting socket The not projecting punctured position to shell 3504 outside（Device pre-implant or afterwards inject state）With grouting socket in patient's body The extended position in shell 3504 outside is completely or partially projected at injection phase on body（Injection state in device） Between vertically move.

Grouting socket support 3502 includes auricle or the pin 3516 extending radially outwardly from support 3502.Auricle 3516 is joined It is set to and interacts with grouting socket latch mechanism 3508 when device is in pre-implant or rear injection state, so that by grouting socket Support 3502 is locked in vertically convex punctured position.Grouting socket protection system 3500 can include being disposed proximate to or connecing The grouting socket latch mechanism 3508 of tactile grouting socket support 3502.In the exemplary embodiment, grouting socket lock 3508 can be The pivot that can pivot around pivotal point or interface 3520 or rotate or rotating member.

Grouting socket protection system 3500 can include the biasing mechanism 3506 being arranged on around biasing mechanism support 3512, Biasing mechanism support 3512 is elongated mechanical component, for example, metal bar or bar.Biasing mechanism support 3512 can be connected to skin Skin sensor foot 3518.Biasing mechanism support 3512 can also be connected to the pivotal point 3514 of grouting socket relieving mechanism 3510, So that rotation under the bias of biasing mechanism 3506 for the biasing mechanism support 3512 makes grouting socket relieving mechanism 3510 rotate around pivotal point 3514.In the exemplary embodiment, grouting socket relieving mechanism 3510 can be and skin sensing The separate part of device foot 3518.In a further exemplary embodiment, grouting socket relieving mechanism 3510 can be skin sensor The part of foot 3518.

Skin sensor foot 3518 can be made convex towards shell 3504 against injection phase apparatus for placing, thus make biasing Mechanism 3506（With biasing mechanism support 3512）It is rotated in a first direction, so that grouting socket relieving mechanism 3510 is pivoted to The position that mechanism 3510 is not interacted with lock mode with grouting socket latch mechanism 3508.Such result is grouting socket Latch mechanism 3508 keeps being in " lower section " position, so that grouting socket support 3502 can move down so that grouting socket Extend to outside shell 3502 to inject therapeutic agent.

Removing device from injection phase makes skin sensor foot 3518 extend or projects into outside shell 3504, thus makes partially Put mechanism 3506（With biasing mechanism support 3512）Rotate in a second direction, so that grouting socket relieving mechanism 3510 also revolves Go to the position interacting with grouting socket latch mechanism 3508 with lock mode.Such result is grouting socket latch mechanism 3508 are rotated to and keep being in D score position, so that grouting socket support 3502 moves and quilt away from injection phase It is locked in position in vertically convex position, so that grouting socket is in punctured position and cannot be used for injecting therapeutic agent.

VI. it is used for keeping aseptic example components in automated injection device and method.

Exemplary embodiment provides and is used for the therapeutic agent in holding meanss and therapeutic agent used in automated injection device The aseptic example components in injection channel, in order to avoid need disinfectant component.Exemplary embodiment also provides to be come using example components Keep aseptic automated injection device and using the automated injection device including this base part in the way of holding meanss are aseptic Method.

Sterile barrier is maintained at the therapeutic agent being included in exemplary automated injection device and therapeutic agent in injection patient Around the injection channel being adopted before and during internal.In the exemplary embodiment, before Plugging agent, can to Carry out disinfection in keeping the syringe of therapeutic agent or the cylindrical portion of injection tube.Aseptic stopper may be located at injector assembly or note To be sealed in therapeutic agent in cylindrical portion in the cylindrical portion of shooting cylinder assembly.Therapeutic agent is by aseptic cylindrical portion and asepsis plug Son is contained in Wearable automatic injection device, and this makes therapeutic agent keep aseptic after device assembling.

Grouting socket button can be arranged between cylindrical portion and grouting socket, for therapeutic agent is injected patient's body Interior.Grouting socket button can include sterile fluid path and be arranged on the aseptic pierceable partition piercing through near syringe needle. Aseptic puncture syringe needle（For example, single syringe needle, multiple syringe needle, needleless liner, needleless paster etc.）Injection can be arranged on connect Near sterile septum in mouthful button, it is in fluid communication for piercing through partition setting up with cylindrical portion.One or more sterility cover Partition can be enclosed in the sterile barrier in grouting socket button.That is, in the exemplary embodiment, aseptic cylindrical part Divide, aseptic puncture syringe needle, sterile septum and partition lid, aseptic grouting socket and grouting socket lid can be to incite somebody to action by collaborative configuration Produce sterile barrier around therapeutic agent before and during therapeutic agent injection in the patient.During injection therapeutic agent, sterile screen Barrier can eliminate patient's needs with alcohol wipe partition before piercing through partition, as is commonly done.

Illustrate and combine Figure 1A and 2A in Figure 1A, 2A, 6A and 7A to describe in this section in automated injection device The middle example components that sterile barrier is provided.In this section with reference to Figure 1A and 2A describe in Fig. 6 A and 8A with Figure 1A and 2A in The part that part is similar to.

For example, the exemplary means 100/200 of Figure 1A/2A include aseptic cylindrical portion 106/206, aseptic puncture syringe needle 120/220th, sterile septum lid 115/215, aseptic grouting socket 118/218（It is illustrated as injection needle）With aseptic grouting socket lid 122/222（It is illustrated as needle cover）.The shell 102/202 of device 100/200 can be included for being attached to shell 102/202 The adhesive layer 126/226 of patient and the protecting film 128/228 for protecting adhesive layer 126/216.In the exemplary embodiment, protect Cuticula 128/228 can be aseptic.Remove protecting film 128/228 and expose adhesive layer 126/216 so that patient can be by inciting somebody to action Have adhesive layer 126/226 that side be placed on body or medicated clothing by shell 102/202 be attached to his or her body or On clothes.

Exemplary automated injection device can be provided with and contribute to removing before injection partition lid and grouting socket lid Part.In some exemplary embodiments, protecting film 128/228 can be provided in an operation or removes in one step Partition lid and the mechanism of grouting socket lid.Protecting film can include being connected to grouting socket lid 122/222 and partition lid 115/215 Coupling member.Coupling member can include tether, auricle or other link mechanism.When protecting film 128/228 is removed, protect The coupling member of cuticula 128/228 can also remove grouting socket lid 122/222 and partition lid 115/215.

Exemplary means can provide different mechanisms to remove protecting film from the shell of device, and thus remove note simultaneously Incoming interface lid and partition lid.In exemplary embodiment shown in Figure 1A and 2A, removing mechanism 130/230, such as auricle, permissible It is arranged on protecting film 128/228, for removing protecting film 128/228 from adhesive layer 126/226.Removing mechanism 130/230 Any part of device package can be not coupled to（For example, transparent overwrap, blister pack, bubble wrap or other business Packaging）, thus protecting film 128/228 remains attached to adhesive layer 126/226 when withdrawing device from the package.Patient can catch And pull removing mechanism 130/230, to remove protecting film 128/228 from adhesive layer 126/226.In the exemplary embodiment, may be used To arrange one or more gripper components at removing mechanism 130/230（For example, ring or veined surface）, in order to catch With pull removing mechanism 130/230.In order to inject therapeutic agent, patient can remove automated injection device from its packaging, and draws Pull removing mechanism 130/230 to remove protecting film 128/228 and to expose adhesive layer 126/226.When pullling removing mechanism 130/230 During removing protecting film 128/228, the coupling member of film 128/228 also removes grouting socket lid 122/222 and partition lid 115/ 215, it is thus prepared for placing the device on patient or his/her clothes, to be injected.

Figure 36 illustrates the another exemplary mechanism for removing protecting film 128 from the shell 102 of device 100, and thus Remove grouting socket lid 122 and partition lid 115.Figure 36 is shown in the example of the Figure 1A being in pre-implant state in outer package 3600 Property device 100.Remove device 130 can be arranged on protecting film 128, for removing protecting film 128 from adhesive layer 126.Move Except mechanism 130 can be attached to the outer package 3600 of device（For example, transparent overwrap, blister pack, bubble wrap or other Commercial packing）Interior section 3602 so that, when from pack withdrawing device when, removing mechanism 130 remains attached to part 3602 and removing mechanism 130 at part 3602 on pull strength remove protecting film 128 from adhesive layer 126.That is, work as dress Put when being entirely located at package outer, remove protecting film 128 from adhesive layer 126, and adhesive layer is ready to be applied to Patient or his/her clothes, to be injected.In order to inject therapeutic agent, patient can take out automatic injection from its packaging Device, this expose adhesive layer 126 and make film 128 coupling member automatically remove grouting socket lid 122, pierce through needle cover and every Piece lid 115, be thus prepared for placing the device in patient or he/its clothes on to be injected.Preparation device so that The method of injection therapeutic agent can reduce the step number of patient's execution and thus reduce the mistake of user.

Figure 37 illustrates the another exemplary mechanism for removing protecting film 228 from the shell 202 of device 200, and thus Remove grouting socket lid 222 and partition lid 215.Figure 37 is shown in the example of the Fig. 2A being in pre-implant state in outer package 3700 Property device 200.Remove device 230 can be arranged on protecting film 228, for removing protecting film 228 from adhesive layer 226.Move Except mechanism 230 can be attached to the outer package 3700 of device（For example, transparent overwrap, blister pack, bubble wrap or other Commercial packing）Interior section 3702 so that, when from pack withdrawing device when, remove device 230 and remain attached to part 3702 and removing mechanism 230 at part 3702 on pull strength remove protecting film 228 from adhesive layer 226.That is, work as dress Put when being entirely located at package outer, remove protecting film 228 from adhesive layer 226, and adhesive layer is ready to be applied to Patient or his/her clothes, to be injected.In order to inject therapeutic agent, patient can take out automatic injection from its packaging Device, this expose adhesive layer 226 and make film 228 coupling member automatically remove grouting socket lid 222, pierce through needle cover and every Piece lid 215, is thus prepared for placing the device on patient or his/her clothes, to be injected.Preparation device so that The method of injection therapeutic agent can reduce the step number of patient's execution and thus reduce the mistake of user.

VII. exemplary grouting socket

Exemplary embodiment is provided and is suitable for being used together with the exemplary automated injection device describing above in association with Fig. 1-37 For by doses therapeutic agent injection exemplary grouting socket in the patient.Exemplary embodiment also provides and uses example Property grouting socket by doses therapeutic agent injection automated injection device in the patient.Exemplary grouting socket can be by one Be arranged in automated injection device or be arranged to the single part that can be connected on automated injection device, such as needleless Paster or attachment.Exemplary grouting socket can be configured for different types of injection, including but not limited to, subcutaneous note Penetrate, corium injection, intramuscular injection, local injection etc..Can be based on one or more factors, including but not limited to application type, Type of therapeutic agent etc., to change the therapeutic agent flow velocity that exemplary embodiment is reached.For example, it is possible to than being locally implanted and corium Inject fast speed and carry out subcutaneous and muscle injection.In the exemplary embodiment, can be connect based on the flow velocity configuration injection requiring Mouthful.For example, it is possible to increase the internal diameter of grouting socket to reach higher therapeutic agent flow velocity.

Exemplary grouting socket can be used for by therapeutic transport to or pass through biological barrier, it includes but is not limited to, skin Skin（Or part thereof）, blood brain barrier, mucosal tissue（For example, oral cavity, nasal cavity, vagina, urethra, gastrointestinal tract, respiratory tract）, blood vessel, Lymphatic vessel, cell membrane etc..Biological barrier may reside in the mankind or other types of animal, and plant, insecticide or other Organism（Including but not limited to, antibacterial, yeast, funguses, embryo etc.）In.Target organism barrier may be located at normally complete In tissue.Target organism barrier may be located in the impaired or tissue of pathological changes, such as wound or diseased region.In conduit and abdominal cavity With the help of mirror, exemplary grouting socket can be applied to tissue outside or inside.For some applications, such as therapeutic agent is noted Enter interior tissue, exemplary grouting socket can be implanted by surgical operation.Exemplary embodiment can be provided using micropin dress Put the grouting socket injecting therapeutic agent through biological barrier.

Exemplary grouting socket can include the one or more skin-piercing parts being configurable for injecting therapeutic agent, Including but not limited to, single syringe needle/microneedle/micropin, multiple syringe needle/microneedle/micropins, are connected to the syringe needle of pipe/miniature Pin/micropin etc..In some exemplary embodiments, used in exemplary grouting socket, microneedle and/or micropin can dissolve.

Exemplary grouting socket can also include being applied to patient so that the needleless being locally implanted of execution therapeutic agent Liner and/or needleless paster.Example components for this kind of application can include and the cylindrical portion fluid comprising therapeutic agent The reservoir of connection and drug osmotic film, this drug osmotic film allows therapeutic agent to pass through this membrane diffusion to skin surface from reservoir On.Other examples part can include elasticity or rigid structure, and this structure forms bag when contacting with skin together with skin, Skin forms a surface of bag.This bag can be filled with the therapeutic agent from reservoir so that therapeutic agent can be in prolongation It is absorbed by the skin in time period or diffuse through skin.In some exemplary embodiments, exemplary grouting socket is being applied Before carrying out topical application to skin, pretreatment can be carried out to skin.

Exemplary grouting socket can be formed by any suitable material, including but not limited to, polymeric material（For example, Medical grade polymer）, metal, glass, silicon crystal etc..Exemplary grouting socket can include hollow and/or have fluid ditch One or more injection needles of groove.

Exemplary grouting socket can have and is suitable to by any suitable method（Including but not limited to, intramuscular injection, office Portion's administration, subcutaneous injection, corium injection etc.）By therapeutic agent injection any suitable size in the patient, shape and configuration.Close Suitable grouting socket can have the length being configured to or being chosen as to provide the injection depth being suitable to required treatment.For example, skin About six to ten millimeters of skin is generally pierced in lower injection.In the exemplary embodiment, grouting socket can have the length of about 12mm And skin can be injected to the depth of about 7mm.

Suitably grouting socket can have and is adapted to provide for the wall thickness of enough mechanical strengths, is adapted to allow for required controlling Treat agent flow velocity to feel to be down to minimum height, diameter and be suitable to required treatment to feel to be down to by patient by patient simultaneously simultaneously Low tip geometry.In the case of pharmaceutically acceptable, suitable grouting socket can be configured to feel patient as required Feel is down to minimum.One or more factors can be based on, including but not limited to, inject type（Subcutaneous, muscle etc.）, Huan Zhenian Age, weight in patients, therapeutic agent etc., to configure length and the thickness of injection needle（gauge）.In some exemplary embodiments, Can have exemplary thickness between about 23 gauge and about 25 gauge for hypodermic injection needle and about Exemplary lengths between 7mm and about 15mm, but not limited to this exemplary range.In some exemplary embodiments, it is used for The injection needle of intramuscular injection can have exemplary thickness between about 22 gauge and about 25 gauge and in about 10mm Exemplary lengths between about 50mm.In some exemplary embodiments, injection needle can be micropin, i.e. prominent at them The surface risen has the structure of about 500 microns or less of height.In some instances, exemplary micropin can have about 250 microns or less of height.

In some exemplary embodiments, as shown in Figure 1A -1F, 2A-2F, 6A-6C, 7A-7C, 15-17,36 and 37, note Incoming interface can include single injection needle.In some other exemplary embodiment, grouting socket can include being connected to one Individual or multiple conduits single injection needle in flow communication.

In the exemplary embodiment, the type and size of grouting socket can be used for configuring one of automated injection device or Many aspects, including but not limited to, shell, the mechanism that device is applied to injection phase, the internal fluid pathway in device and Geometry etc..

VIII. the merging quoted

Run through whole substance quoteds that the application quotes（Including patents and patent applicationss）Full content by quoting conjunction And in this.These suitable parts in quoting and method can be alternatively used for the present invention and embodiment.Additionally, in the back of the body The clear and definite part of scape technology segment and method are part of the whole of the present invention and within the scope of the invention can be with this The part of bright other local description and method combine or replace them.

Ⅸ. equivalent description

When describing exemplary embodiment, use particular term for clarity.For the sake of describing, each specific art Meaning of one's words figure at least includes being operated and then realized similar all technology of purpose and the equivalent description of function in a similar manner.This Outward, in some examples that certain exemplary embodiments include multiple system elements or method and step, these elements and step can To be substituted by discrete component or step.Similarly, discrete component or step can be used for multiple element or the step of identical purpose Rapid replacement.Additionally, when the parameter of the various performances in this paper embodied examples embodiment, these parameters can be tuned up or Turn 1/20,1/10,1/5,1/3,1/2 etc. down or tuned up or turn down the approximation that rounds up, unless otherwise stated.Additionally, Although illustrate and describing exemplary embodiment, those of ordinary skill in the art with reference to only certain embodiments of the present invention It should be understood that without departing from the scope of the invention can be in the form of to the present invention and details carries out various replacing and changing Become.Additionally, other side, function and advantage are also within the scope of the invention.

Exemplary process diagram is example that provide for purpose of illustration and not method for limiting.Ordinary skill Personnel, and can it should be understood that illustrative methods can include more or less of step shown in exemplary process diagram for the ratio With the step by executing exemplary flow in figure from shown different order.

Claims (41)

1. a kind of do not need battery for by therapeutic agent injection Wearable automatic injection device in the patient, described wear The formula automated injection device of wearing includes：

Shell, it includes the patient contacting portions with the contraction trigger being configured to contact patient, and described contraction trigger rings Should operate from injection state to the state change of rear injection state in Wearable automatic injection device；

Fill assembly, it is movably disposed in shell, keeps being configured to the injection in the patient by therapeutic agent injection and connects Mouthful, this fill assembly can project into stretching outside shell in the not projecting punctured position to outside shell of grouting socket and grouting socket Exhibition position is moved between putting；

Container, it is arranged in shell, and is configured to preserve therapeutic agent；And

Piston actuated mechanism, it is movably disposed in described container, and is configured to inject to therapeutic agent from container In fill assembly；And

Contracting mechanism, its be configured by described shrink trigger triggering make fill assembly from injection state extended position from Move the punctured position injecting state after being retracted to；

Wherein, the therapeutic agent between 0.1 milliliter and 1.0 milliliters is amassed within the time less than 30 seconds from container emitting body.

2. Wearable automatic injection device according to claim 1, wherein, described container includes syringe.

3. Wearable automatic injection device according to claim 2, wherein, described syringe includes：

For preserving the cylindrical portion of therapeutic agent；And

Pierce through syringe needle, it is connected to the far-end of cylindrical portion, is configured to build between the cylindrical portion of syringe and fill assembly Vertical fluid communication.

4. Wearable automatic injection device according to claim 3, wherein, described fill assembly includes：

The partition of the puncture needle pierces of device can be injected；And

The fluid conduit systems extending between grouting socket and partition, wherein, can will be noted with the puncture needle pierces partition of syringe The cylindrical portion of emitter and grouting socket are linked together.

5. Wearable automatic injection device according to claim 4, wherein, when described device is in pre-implant state When, puncture syringe needle and the separates of described syringe are opened, and wherein, when described device is in injection state, described thorn Wear needle pierces partition.

6. Wearable automatic injection device according to claim 1, wherein, described container includes injection tube.

7. Wearable automatic injection device according to claim 6, wherein, described injection tube includes：

It is configured to preserve the cylindrical portion of therapeutic agent；And

The partition of needle pierces can be pierced.

8. Wearable automatic injection device according to claim 7, wherein, described fill assembly includes：

Pierce through syringe needle, it is configured to set up between the cylindrical portion of injection tube and grouting socket and is in fluid communication；And

Fluid conduit systems, it is arranged on grouting socket and pierces through between syringe needle, is configured to the tubular in grouting socket and injection tube Set up between part and be in fluid communication.

9. Wearable automatic injection device according to claim 8, wherein, with the puncture needle pierces of fill assembly every Fluid communication is set up in sector-meeting between the cylindrical portion of injection tube and grouting socket.

10. Wearable automatic injection device according to claim 9, wherein, when described device is in pre-implant state When, the partition of described injection tube is separated with the puncture syringe needle of fill assembly, and wherein, when described device is in injection state When, described puncture needle pierces partition.

11. Wearable automatic injection device according to claim 1, wherein, described container is movably disposed on Inside the shell.

12. Wearable automatic injection device according to claim 11, wherein, described container can be in pre-implant state Primary importance and injection state the second position between move.

13. Wearable automatic injection device according to claim 12, further include：

Container actuators, it is used for for container being automatically actuated into the second position from primary importance.

14. Wearable automatic injection device according to claim 13, wherein, when fill assembly is in extended position simultaneously And described container be in injection state the second position when, set up fluid passage between fill assembly and described container.

15. Wearable automatic injection device according to claim 1, wherein, described piston actuated mechanism is with controlled Therapeutic agent is injected in the patient by linear velocity.

16. Wearable automatic injection device according to claim 1, wherein, described piston actuated mechanism is wrapped further Include：

Piston, it is configured to apply expulsion force to the therapeutic agent in container；

Workflow body source, it is configured to provide hydraulic pressure to piston；And

Fluid conduit systems, it is arranged between workflow body source and piston.

17. Wearable automatic injection device according to claim 16, wherein, described piston actuated mechanism is wrapped further Include：

Damping mechanism, it is coupled to piston and workflow body source, with adjustment for the treatment of agent from the injection of container.

18. Wearable automatic injection device according to claim 17, wherein, described damping mechanism includes flow restriction Device, the first hydraulic pressure that this flow restrictor is configured to retain towards the flow restrictor downstream of container is less than towards workflow Second hydraulic pressure of the flow restrictor upstream of body source.

19. Wearable automatic injection device according to claim 18, wherein, described flow restrictor is connected to contraction Trigger, wherein, the injection of the therapeutic agent in container makes flow restrictor start contraction trigger, and wherein, shrinks triggering The startup of device makes fill assembly automatically be retracted to punctured position from extended position.

20. Wearable automatic injection device according to claim 1, further include：

Grouting socket locking mechanism, it is configured to automatically lock outside grouting socket in pre-implant state and rear injection state Punctured position in shell.

21. Wearable automatic injection device according to claim 20, wherein, described grouting socket locking mechanism bag Include：

Barrier mechanism, on its grouting socket breach being movably disposed in shell；

Wherein, when described barrier mechanism is in primary importance, described grouting socket breach allows grouting socket to project into shell Outward；And

Wherein, when described barrier mechanism is in the second position, described grouting socket breach stops grouting socket from projecting into shell Outward.

22. Wearable automatic injection device according to claim 20, wherein, described grouting socket locking mechanism bag Include：

Grouting socket locks relieving mechanism, its contraction from the extended position of injection state to rear injection state in response to fill assembly The contraction of position and operate；And

Pivot member, it is connected to grouting socket and is connected to grouting socket lock relieving mechanism；

Wherein, the startup of grouting socket lock relieving mechanism makes the injection that pivot member pivot grouting socket makes it away from shell connect Mouth breach.

23. Wearable automatic injection device according to claim 1, wherein, described therapeutic agent includes TNF α inhibitor.

24. Wearable automatic injection device according to claim 1, wherein, by therapeutic agent add in a reservoir it Afterwards, sterile barrier is maintained at the note comprising that therapeutic agent in a reservoir and therapeutic agent are being adopted during being injected in the patient Enter around passage.

25. Wearable automatic injection device according to claim 24, wherein it is not necessary to automated injection device aseptic Assembling is to keep therapeutic agent, one or more skins of grouting socket pierce surface and therapeutic agent during being injected in the patient The injection channel being adopted is aseptic.

26. Wearable automatic injection device according to claim 24, wherein, provide described sterile screen by components described below Barrier：

The aseptic cylindrical portion being configured to preservation therapeutic agent of described container；

It is configured to set up the aseptic puncture syringe needle of fluid conduit systems between the cylindrical portion of container and grouting socket；

The sterile septum that needle pierces can be pierced of fill assembly；

The sterile fluid conduit of the fill assembly extending between grouting socket and partition, wherein uses the puncture needle pierces of container Partition sets up fluid communication between the cylindrical portion of container and grouting socket；And

Aseptic grouting socket.

27. Wearable automatic injection device according to claim 26, further include：

For covering and keeping the aseptic partition lid of partition；

It is configured to the grouting socket lid covering and holding grouting socket is aseptic with the fluid conduit systems being connected to grouting socket；And

For covering and keeping piercing through syringe needle the puncture needle cover aseptic with the fluid conduit systems being connected to puncture syringe needle.

28. Wearable automatic injection device according to claim 27, further include：

Protecting film, it is attached at least one portion of shell, and described protecting film is connected to partition lid, grouting socket lid and thorn Thread a needle skull, so that remove protecting film from shell and automatically removing partition lid, grouting socket lid and pierce through needle cover.

29. Wearable automatic injection device according to claim 28, wherein, described protecting film includes：

Attachment means, it is attached to the packaging preserving automated injection device, so that taking out automated injection device meeting from packaging Remove protecting film from the shell of automated injection device, remove protecting film and can remove partition lid, grouting socket lid and pierce through needle cover.

30. Wearable automatic injection device according to claim 28, wherein, described protecting film includes:

Removing mechanism, it is configured to be pullled, to remove protecting film from the shell of automated injection device, removes protecting film meeting Remove partition lid, grouting socket lid and pierce through needle cover.

31. Wearable automatic injection device according to claim 1, wherein, described grouting socket is needleless paster.

A kind of method of Wearable automatic injection device according to any one of claims 1 to 31 for 32. assemblings, described Method includes：

Assemble the Part I of automated injection device in gnotobasiss, to preserve the sterile treatment agent of doses；

There is provided the one or more sterile barrier parts related to the Part I of automated injection device, with assembling automatic injection Keep the fluid passage that therapeutic agent is adopted during being injected in the patient aseptic during and after device；And

The Part II of automated injection device, wherein, the Part I of described automated injection device is assembled in ambient non-sterile Including container, the Part II of described automated injection device includes piston actuated mechanism.

33. methods according to claim 32, wherein, the Part I assembling described automated injection device includes：

Fill assembly is assembled in the shell of automated injection device, is configured to holding and is configured to inject in the patient therapeutic agent Aseptic grouting socket, described fill assembly can be in the not projecting contraction to outside the shell of automated injection device of grouting socket Move between the extended position that position and grouting socket project into outside the shell of automated injection device；And

Described container is assembled in the shell of automated injection device, described container structure becomes to preserve therapeutic agent.

34. methods according to claim 33, wherein, described container is syringe.

35. methods according to claim 34, wherein, assemble described syringe and include：

The aseptic cylindrical portion being configured to the syringe preserving therapeutic agent is provided；

Proximal part using aseptic plug seal cylindrical portion；

Aseptic is pierced through the far-end that syringe needle is connected to cylindrical portion, so that between the cylindrical portion of syringe and grouting socket Set up and be in fluid communication；And

Cover aseptic puncture syringe needle with the aseptic needle cover that pierces through；

Wherein, aseptic cylindrical portion, aseptic stopper, aseptic puncture syringe needle and aseptic puncture needle cover provide sterile screen Barrier, so that the fluid passage in syringe keeps aseptic during and after assembling automated injection device.

36. methods according to claim 35, wherein, assemble described fill assembly and include：

There is provided aseptic grouting socket lid for aseptic grouting socket；

Offer can be injected the aseptic partition of the puncture needle pierces of device；

Cover aseptic partition with aseptic partition lid, to keep aseptic partition aseptic；And

There is provided the aseptic fluid conduit systems extending between aseptic grouting socket and aseptic partition, wherein, with syringe Pierce through needle pierces partition the cylindrical portion of syringe and grouting socket can be linked together；

Wherein, aseptic grouting socket, aseptic grouting socket lid, aseptic partition, aseptic partition lid and aseptic fluid Conduit provides makes the fluid passage in fill assembly keep aseptic sterile barrier during and after assembling automated injection device.

37. methods according to claim 33, wherein, described container is injection tube.

38. methods according to claim 37, wherein, assemble described injection tube and include：

The aseptic cylindrical portion being configured to preserve therapeutic agent is provided；

Proximal part using aseptic plug seal cylindrical portion；

It is possible to be connected to the far-end of cylindrical portion by the aseptic partition of aseptic puncture needle pierces；And

Cover aseptic partition with aseptic partition lid；

Wherein, aseptic cylindrical portion, aseptic stopper, aseptic partition and aseptic partition lid provide sterile barrier, so that Fluid passage in injection tube keeps aseptic during and after assembling automated injection device.

39. methods according to claim 38, wherein, assemble described fill assembly and include：

Cover aseptic grouting socket with aseptic grouting socket lid；

Pierce through the proximal part that syringe needle is connected to fill assembly by aseptic, so that in the cylindrical portion of injection tube and grouting socket Between set up be in fluid communication；

Cover aseptic puncture syringe needle with the aseptic needle cover that pierces through；And

There is provided in aseptic grouting socket and the aseptic aseptic fluid conduit systems piercing through between syringe needle, so as in grouting socket and Set up between the cylindrical portion of injection tube and be in fluid communication；

Wherein, aseptic grouting socket, aseptic grouting socket lid, aseptic puncture syringe needle, aseptic puncture needle cover and nothing The fluid conduit systems of bacterium provide makes the fluid passage in fill assembly keep aseptic during and after assembling automated injection device Sterile barrier.

40. methods according to claim 32, wherein, the therapeutic agent of doses are being added to automated injection device After in Part I, sterile barrier is maintained at the therapeutic agent being included in automated injection device and therapeutic agent and is being injected into trouble Around the fluid passage being adopted during in person's body.

41. methods according to claim 40, wherein it is not necessary to sterilely assemble the Part II of automated injection device, Fluid to keep the therapeutic agent being included in automated injection device and therapeutic agent to be adopted during being injected in the patient leads to The sterile barrier of the surrounding in road.